LITERATURE REVIEW - McMaster University



MEASUREMENT OF BROWN ADIPOSE TISSUE USING MRI IN ADULT HUMANSMEASUREMENT OF BROWN ADIPOSE TISSUE USING MRI IN ADULT HUMANSBy FRANK JOSEPH ONG, B.Sc.A Thesis Submitted to the School of Graduate Studies in Partial Fulfilment of the Requirements for the Degree Master of SciencesMcMaster University ? Copyright by Frank Joseph Ong, November 2017MASTER OF SCIENCES (Department Medical Sciences, 2017)McMaster University, Hamilton, OntarioTITLE: Measurement of Brown Adipose Tissue Using MRI in Adult Humans AUTHOR: Frank Joseph Ong, B.Sc. (McMaster University) SUPERVISOR: Dr. Katherine Morrison COMMITTEE: Dr. Katherine Morrison, Dr. Gregory Steinberg and Dr. Zubin PunthakeeNUMBER OF PAGES: xviii, 145AbstractBACKGROUND: There has been renewed interest in the study of brown adipose tissue (BAT) as a potential therapeutic target for obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). There is now much evidence to suggest that BAT is not only important in thermogenesis but also plays an important role in metabolism ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db15-0146", "ISBN" : "0012-1797", "ISSN" : "1939327X", "PMID" : "26050667", "abstract" : "Brown adipose tissue (BAT) is a unique tissue that is able to convert chemical energy directly into heat when activated by the sympathetic nervous system. While initially believed to be of relevance only in human newborns and infants, research during recent years provided unequivocal evidence of active BAT in human adults. Moreover, it has become clear that BAT plays an important role in insulin sensitivity in rodents and humans. This has opened the possibility for exciting new therapies for obesity and diabetes. This review summarizes the current state of research with a special focus on recent advances regarding BAT and insulin resistance in human adults. Additionally, we provide an outlook on possible future therapeutic uses of BAT in the treatment of obesity and diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Betz", "given" : "Matthias J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2352-2360", "title" : "Human brown adipose tissue: What we have learned so far", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1. In adults, cold-induced BAT activation has led to a significant increase in insulin sensitivity and energy expenditure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.3891", "ISBN" : "1546-170X", "ISSN" : "1078-8956", "PMID" : "26147760", "abstract" : "Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 \u00b0C) increased peripheral insulin sensitivity by \u223c43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, without effects on insulin signaling or AMP-activated protein kinase (AMPK) activation and only a minor increase in BAT glucose uptake.", "author" : [ { "dropping-particle" : "", "family" : "Hanssen", "given" : "Mark J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeks", "given" : "Joris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "Boudewijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lans", "given" : "Anouk A J J", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schaart", "given" : "Gert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Driessche", "given" : "Jos\u00e9 J", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f6rgensen", "given" : "Johanna A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Boekschoten", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hesselink", "given" : "Matthijs K C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Havekes", "given" : "Bas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kersten", "given" : "Sander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottaghy", "given" : "Felix M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "8", "6" ] ] }, "page" : "863-865", "title" : "Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db14-0746/-/DC1", "ISBN" : "4163612661", "ISSN" : "1939327X", "PMID" : "25056438", "abstract" : "Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. 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Thus, it is important to identify factors associated with these metabolic disorders such as the presence and activity of BAT to better understand if and how BAT can be targeted to treat these disorders. However, as a potential therapeutic target, it is important to develop accurate, precise, robust and reproducible non-invasive modalities to measure BAT. PROJECT OBJECTIVES: 1) Develop and assess protocols for the use of MRI in measuring BAT characteristics and activity2) Examine the relationship between BAT MR outcomes and known covariates such as age, sex, body fat percentage and outdoor temperature in adult humans3) Determine if there is any association between BAT outcomes and liver fat in adult humans, before and after adjusting for potential covariates of liver fat such as age, sex and body fat percentage METHODS: In total, 36 healthy participants (i.e. no conditions or medications that could influence BAT metabolism and/or liver disease) aged 18 to 60 years were recruited to this cross-sectional study. There were two study visits. In visit 1, anthropometrics (i.e. height, weight and waist circumference), blood pressure and body composition (via dual x-ray energy absorptiometry) were measured. Additionally, fasting bloodwork was collected and a 75-g oral glucose tolerance test (OGTT) was administered. During visit 2, participants were exposed to a standardized cold exposure set at 18°C for 3 hours using a water-perfused suit. MRI scans were acquired to evaluate changes in fat-fraction (FF%) and T2* relaxation (T2*) (BAT MR outcomes), liver fat and abdominal fat after a cold exposure. During the cold exposure protocol, mean skin temperature (MST) was monitored using 12 wireless temperature loggers placed at different sites of the body while electromyography (EMG) was used to measure shivering intensity. RESULTS: In the current study, an MRI protocol capable of detecting BAT in the supraclavicular (SCV) region was developed. This protocol included the use of FF and T2* masks to more accurately characterize BAT in the SCV region. Additionally, the MR segmentation protocol was found to be very reliable, as demonstrated by excellent ICC values (i.e. ICCagreement and ICCconsistency ≥ 0.90) for all BAT MR outcomes irrespective of cold exposure. As expected, FF% (mean difference = -2.97; p < 0.0001*) and T2* (mean difference = -0.84; p < 0.0001*) values in the SCV significantly decreased after cold exposure, consistent with BAT activation. Furthermore, the decline in both FF% and T2* after cooling was specific to the SCV region, as these changes did not occur in the posterior neck fat. In examining the relationship between BAT MR outcomes and known covariates of BAT (i.e. age, sex, body fat percentage and outdoor temperature), it is important to note that lower FF% or T2* values are reflective of a browner phenotype while a greater reduction in FF% is indicative of higher BAT activity. BAT characteristics (A: pre-cold FF%; B: pre-cold T2*) and BAT activity (C: FF% reduction) were correlated with age (A: r = 0.54; p = 0.0007*; B: r = 0.42; p = 0.0112*; C: r = -0.39; p = 0.0213*) and body fat percentage (A: r = 0.83; p < 0.0001*; B: r = 0.58; p = 0.0002*; C: r = -0.64; p < 0.0001*). That is, higher age and body fat were associated with a less brown phenotype prior to cold exposure and with less BAT activity (i.e. lower FF% decline) in response to cold exposure. However, no associations were found between BAT MR outcomes and sex or outdoor temperature. Lastly, liver fat was associated with higher values of pre-cold FF% (r = 0.60; p < 0.0001*) and pre-cold T2* (r = 0.47; p = 0.0040*) while FF% reduction was inversely correlated with liver fat (r = -0.38; p = 0.0295*). Additionally, the relationship between BAT MR outcomes and liver fat still existed after adjusting for age and sex while its effects were mediated by adiposity. CONCLUSION: In this study, a highly reliable MR segmentation protocol was developed that is capable of measuring BAT characteristics and activity irrespective of cold exposure. Additionally, the cold exposure protocol used was sufficient to elicit changes in BAT MR outcomes, as demonstrated by significant changes in FF% and T2* after cooling. Consistent with previous studies, BAT outcomes (as measured by MRI) were associated with age and body fat percentage. Lastly, findings in this thesis provide strong supporting data that BAT may regulate liver lipid content, however, the extent and mechanisms remain to be determined. Acknowledgements This journey (aka “thesis life”) would have not been possible without the constant support and guidance of many people who I have met along the way. I would like to express my deepest gratitude to Dr. Katherine Morrison, who has been an endless source of inspiration and knowledge over the past four years. What started as a typical research assistant position in undergrad quickly developed into a passion for research. Throughout this journey, I have developed countless skills and have grown as a researcher and as a person. I would also like to thank members of my supervisory committee, Dr. Gregory Steinberg and Dr. Zubin Punthakee, for your knowledge, insights and critiques that have made this project not only possible but as robust as it can be. I am especially lucky and grateful to be surrounded with an amazing and supportive team. “Lab life” wouldn’t have been as much fun and exciting without all of you folks! I would like to think that everyone contributed “equally” into making this journey awesome but I would first like to thank the GET-BAT team who have endured quite some big bumps with me throughout this journey starting with Elizabeth Gunn, Stephanie Schwindt, Basma Ahmed, Stephan Oreskovich and Emily Hutchings. Special thanks to Vivian Vaughan Williams for her constant support throughout my time in the lab. And the following people for being themselves (i.e. awesome): Jen Li and Efrah Yousuf. I would also like to acknowledge Norman Konyer, Dr. Mike Noseworthy, Dr. Nina Singh, Dr. Francois Haman and Dr. Denis Blondin for their assistance in developing this project. And finally, I am grateful to my family, who have been nothing but supportive during this time. Thank you for listening to my complaints and for your constant encouragement while I undertook this journey! Table of Contents TOC \o "1-5" \h \z \u CHAPTER 1. LITERATURE REVIEW PAGEREF _Toc499791786 \h 11.1Brown Adipose Tissue PAGEREF _Toc499791787 \h 11.1.1Background PAGEREF _Toc499791788 \h 11.1.2Location PAGEREF _Toc499791789 \h 11.1.3Origin and Development PAGEREF _Toc499791790 \h 21.1.4Morphology PAGEREF _Toc499791791 \h 31.2Factors associated with BAT PAGEREF _Toc499791792 \h 31.2.1BMI and Adiposity PAGEREF _Toc499791793 \h 41.2.2Age PAGEREF _Toc499791794 \h 41.2.3Sex PAGEREF _Toc499791795 \h 41.2.4Outdoor temperature PAGEREF _Toc499791796 \h 51.3IMAGING MODALITIES TO DETECT BAT PAGEREF _Toc499791797 \h 51.3.118F-FDG PET-CT PAGEREF _Toc499791798 \h 61.3.2MRI PAGEREF _Toc499791799 \h 71.3.2.1 BAT MR Characteristics PAGEREF _Toc499791800 \h 71.3.2.2 BAT MR Activity PAGEREF _Toc499791801 \h 81.4Non-Alcoholic Fatty Liver Disease PAGEREF _Toc499791802 \h 81.4.1Background PAGEREF _Toc499791803 \h 81.5Risk factors associated with NAFLD PAGEREF _Toc499791804 \h 91.5.1Obesity and Metabolic Syndrome PAGEREF _Toc499791805 \h 91.5.2Sex PAGEREF _Toc499791806 \h 101.5.3Race and Genetic Factors PAGEREF _Toc499791807 \h 101.6Link between BAT and Nafld PAGEREF _Toc499791808 \h 11CHAPTER 2. STUDY DESIGN PAGEREF _Toc499791809 \h 132.1Rationale PAGEREF _Toc499791810 \h 132.2Significance PAGEREF _Toc499791811 \h 142.3Objectives PAGEREF _Toc499791812 \h 142.4GET-BAT Study Methodology PAGEREF _Toc499791813 \h 152.4.1Inclusion / Exclusion Criteria PAGEREF _Toc499791814 \h 152.4.2Subject Recruitment PAGEREF _Toc499791815 \h 162.4.3Study Visits PAGEREF _Toc499791816 \h 162.4.4Visit Timelines PAGEREF _Toc499791817 \h 192.5Project Recruitment PAGEREF _Toc499791818 \h 20CHAPTER 3. DevelopMENT AND ASSESSMENT OF MRI protocols IN MEASURING BAT characteristics and activity (OBJECTIVE 1) PAGEREF _Toc499791819 \h 213.1INTRODUCTION PAGEREF _Toc499791820 \h 22PART 1. DEVELOPMENT AND DESIGN OF PROTOCOL TO MEASURE BAT CHARACTERISTICS AND ACTIVITY USING MRI PAGEREF _Toc499791821 \h 233.2BACKGROUND PAGEREF _Toc499791822 \h 243.3METHODS PAGEREF _Toc499791823 \h 253.3.1Development of BAT MRI Acquisition Protocol PAGEREF _Toc499791824 \h 253.3.2Development of BAT MRI Analysis and Segmentation Protocol PAGEREF _Toc499791825 \h 263.3.3Reliability Measurement of MRI Segmentation Protocol PAGEREF _Toc499791826 \h 303.3.4Statistical Analysis PAGEREF _Toc499791827 \h 303.4RESULTS PAGEREF _Toc499791828 \h 333.4.1Development of BAT MRI Analysis and Segmentation Protocol PAGEREF _Toc499791829 \h 333.4.2Reliability of BAT MR Segmentation Protocol PAGEREF _Toc499791830 \h 383.5DISCUSSION PAGEREF _Toc499791831 \h 413.5.1Evaluating BAT FF% Threshold PAGEREF _Toc499791832 \h 413.5.2Evaluating BAT T2* Threshold PAGEREF _Toc499791833 \h 423.5.3Inter-Rater Segmentation Reliability PAGEREF _Toc499791834 \h 43PART 2. ASSESSMENT OF THE NEWLY DEVELOPED PROTOCOL TO MEASURE BAT CHARACTERISTICS AND ACTIVITY PAGEREF _Toc499791835 \h 443.6BACKGROUND PAGEREF _Toc499791836 \h 453.7METHODS PAGEREF _Toc499791837 \h 453.7.1Anthropometrics PAGEREF _Toc499791838 \h 453.7.2Body Composition PAGEREF _Toc499791839 \h 463.7.3Outdoor Temperature PAGEREF _Toc499791840 \h 473.7.4Cold Exposure Protocol PAGEREF _Toc499791841 \h 473.7.5Abdominal Subcutaneous Adipose Tissue PAGEREF _Toc499791842 \h 473.7.6Posterior Neck SAT PAGEREF _Toc499791843 \h 483.7.7Statistical Analysis PAGEREF _Toc499791844 \h 493.8RESULTS PAGEREF _Toc499791845 \h 503.8.1Participant Demographics PAGEREF _Toc499791846 \h 503.8.2Comparison of MR Characteristics in Various Fat Pads PAGEREF _Toc499791847 \h 513.8.3Effects of Cold Exposure on MR Outcomes in the SCV or Posterior Neck PAGEREF _Toc499791848 \h 523.8.4Ability to Predict BAT Activity without Cold Exposure PAGEREF _Toc499791849 \h 543.9DISCUSSION PAGEREF _Toc499791850 \h 563.9.1Comparison of MR Characteristics in Various Fat Pads PAGEREF _Toc499791851 \h 563.9.2Effects of Cold Exposure on MR Outcomes in the SCV or Posterior Neck PAGEREF _Toc499791852 \h 573.9.3Ability to Predict BAT Activity without Cold Exposure PAGEREF _Toc499791853 \h 60CHAPTER 4. examination of the relationship between bat characteristics and activity and known covariates (OBJECTIVE 2) PAGEREF _Toc499791854 \h 624.1BACKGROUND PAGEREF _Toc499791855 \h 634.2METHODS PAGEREF _Toc499791856 \h 634.2.1Primary Outcome PAGEREF _Toc499791857 \h 634.2.2Known Covariates PAGEREF _Toc499791858 \h 644.2.3Statistical Analysis PAGEREF _Toc499791859 \h 644.3RESULTS PAGEREF _Toc499791860 \h 664.3.1Participant Demographics PAGEREF _Toc499791861 \h 664.3.2Relationship between BAT MR Outcomes and Known Covariates PAGEREF _Toc499791862 \h 674.3.2.1 BAT and Age PAGEREF _Toc499791863 \h 674.3.2.2 BAT and % Body Fat PAGEREF _Toc499791864 \h 684.3.2.3 BAT and Sex PAGEREF _Toc499791865 \h 694.3.2.4 BAT and Outdoor Temperature PAGEREF _Toc499791866 \h 704.3.3Multiple Regression Model PAGEREF _Toc499791867 \h 704.3.3.1 Pre-Cold FF% PAGEREF _Toc499791868 \h 714.3.3.2 Pre-Cold T2* PAGEREF _Toc499791869 \h 724.3.3.3 FF% Reduction PAGEREF _Toc499791870 \h 734.4Discussion PAGEREF _Toc499791871 \h 744.4.1BAT and Age PAGEREF _Toc499791872 \h 744.4.2BAT and Adiposity PAGEREF _Toc499791873 \h 754.4.3BAT and Sex PAGEREF _Toc499791874 \h 764.4.4BAT and Outdoor Temperature PAGEREF _Toc499791875 \h 774.4.5Multiple Regression Model PAGEREF _Toc499791876 \h 784.4.6Interpretation of BAT MR Outcomes PAGEREF _Toc499791877 \h 79CHAPTER 5. examination of the relationship between bat (characteristicS and activity) and liver fat (OBJECTIVE 3) PAGEREF _Toc499791878 \h 815.2BACKGROUND PAGEREF _Toc499791879 \h 825.3METHODS PAGEREF _Toc499791880 \h 825.3.1Primary Outcome PAGEREF _Toc499791881 \h 825.3.2Exposure Outcome PAGEREF _Toc499791882 \h 835.3.3Potential Covariates PAGEREF _Toc499791883 \h 845.3.4Statistical Analysis PAGEREF _Toc499791884 \h 845.4RESULTS PAGEREF _Toc499791885 \h 855.4.1Participant Demographics PAGEREF _Toc499791886 \h 855.4.2Relationship between BAT and Liver Fat PAGEREF _Toc499791887 \h 875.4.3Multiple Regression Model PAGEREF _Toc499791888 \h 885.4.3.1 Pre-Cold FF% and Liver Fat % PAGEREF _Toc499791889 \h 895.4.3.2 Pre-Cold T2* and Liver Fat % PAGEREF _Toc499791890 \h 915.4.3.3 FF% Reduction and Liver Fat % PAGEREF _Toc499791891 \h 925.6DISCUSSION PAGEREF _Toc499791892 \h 94CHAPTER 6. CONCLUSION PAGEREF _Toc499791893 \h 976.1SUMMARY OF FINDINGS PAGEREF _Toc499791894 \h 976.2LIMITATIONS PAGEREF _Toc499791895 \h 996.3FUTURE DIRECTIONS PAGEREF _Toc499791896 \h 100CHAPTER 7. APPENDIX PAGEREF _Toc499791897 \h 1027.1SUPPLEMENTARY FIGURES AND TABLES (METHODS) PAGEREF _Toc499791898 \h 1027.1.1List of Variables PAGEREF _Toc499791899 \h 1027.1.2MRI Literature Tables PAGEREF _Toc499791900 \h 1047.1.3Exclusion Criteria PAGEREF _Toc499791901 \h 1077.1.4MR Parameters PAGEREF _Toc499791902 \h 1137.1.5MRI Segmentation Protocol PAGEREF _Toc499791903 \h 1157.2SUPPLEMENTARY FIGURES AND TABLES (RESULTS) PAGEREF _Toc499791904 \h 1177.2.1Comparison of FF% Distribution PAGEREF _Toc499791905 \h 1177.2.2Inter-Rater Reliability PAGEREF _Toc499791906 \h 1297.2.3Relationship between T2* Reduction and Known Covariates PAGEREF _Toc499791907 \h 1317.2.4Evaluation of Cold Exposure Protocol in Stimulating BAT Activity PAGEREF _Toc499791908 \h 1337.2.5Interpretation of BAT MR Outcomes PAGEREF _Toc499791909 \h 134CHAPTER 8. BIBLIOGRAPHY PAGEREF _Toc499791910 \h 136List of Figures TOC \h \z \t "Figure" \c Figure 1. Known sites of BAT activation in adult humans according to 18-fluorodeoxyglucose (18F-FDG) uptake PAGEREF _Toc498861982 \h 2Figure 2. Visit 1 Timeline (McMaster University Medical Centre). PAGEREF _Toc498861983 \h 19Figure 3. Visit 2 Timeline (St. Joseph’s Healthcare Hamilton). PAGEREF _Toc498861984 \h 19Figure 4. GET-BAT Adult Cohort Recruitment Flow Chart. PAGEREF _Toc498861985 \h 20Figure 5. Sagittal view of the start (C5/C6 disc) and end (T1/T2 disc) of BAT segmentation. PAGEREF _Toc498861986 \h 28Figure 6. Multi-slice segmentation of the SCV region: left (start of segmentation), right (middle of segmentation) and bottom (end of segmentation). PAGEREF _Toc498861987 \h 28Figure 7. Comparison of the change in FF% between a narrow and broad threshold. PAGEREF _Toc498861988 \h 34Figure 8. Single-slice segmentation at the L4-L5 disc where SAT (red), VAT (green) and RPAT (yellow). PAGEREF _Toc498861989 \h 48Figure 9. Comparison of SCV BAT FF% and SCV BAT T2* before and after cold exposure. PAGEREF _Toc498861990 \h 53Figure 10. Comparison of Posterior Neck SAT FF% and Posterior Neck SAT T2* before and after cold exposure. PAGEREF _Toc498861991 \h 54Figure 11. Correlation between pre-cold FF% and FF% reduction. PAGEREF _Toc498861992 \h 54Figure 12. Correlation between pre-cold T2* and T2* reduction. PAGEREF _Toc498861993 \h 55Figure 13. BAT MR characteristics and age PAGEREF _Toc498861994 \h 68Figure 14. FF% reduction and age PAGEREF _Toc498861995 \h 68Figure 15. BAT MR characteristics and body fat percentage PAGEREF _Toc498861996 \h 69Figure 16. FF% reduction and body fat percentage PAGEREF _Toc498861997 \h 69Figure 17. Fat fraction map (left) and water-related image (right) of the liver. PAGEREF _Toc498861998 \h 83Figure 18. BAT MR characteristics and liver fat PAGEREF _Toc498861999 \h 87Figure 19. FF% reduction and liver fat PAGEREF _Toc498862000 \h 88List of Tables TOC \h \z \t "Table" \c "Table" Table 1. Participant demographics (first 10 participants) PAGEREF _Toc498862001 \h 33Table 2. Participant demographics (High BAT) PAGEREF _Toc498862002 \h 35Table 3. Participant demographics (Low BAT) PAGEREF _Toc498862003 \h 36Table 4. Comparison of BAT MR outcomes with and without T2* mask (n = 10). PAGEREF _Toc498862004 \h 37Table 5. SCV WAT volume in participants with high BAT activity. PAGEREF _Toc498862005 \h 38Table 6. SCV WAT volume in participants with low BAT activity. PAGEREF _Toc498862006 \h 38Table 7. Reliability of SCV BAT FF% between three raters before and after cold exposure PAGEREF _Toc498862007 \h 39Table 8. Reliability of SCV BAT R2* between three raters before and after cold exposure PAGEREF _Toc498862008 \h 39Table 9. Reliability of SCV Volume between three raters before and after cold exposure PAGEREF _Toc498862009 \h 40Table 10. Participant Demographics (entire study cohort; n=36) PAGEREF _Toc498862010 \h 51Table 11. Comparison of MR characteristics between SCV BAT and posterior neck SAT. PAGEREF _Toc498862011 \h 52Table 12. Comparison of MR characteristics between SCV BAT and abdominal SAT. PAGEREF _Toc498862012 \h 52Table 13. Participant Demographics (Objective 2) PAGEREF _Toc498862013 \h 66Table 14. BAT MR outcomes and sex PAGEREF _Toc498862014 \h 70Table 15. BAT MR outcomes and outdoor temperature PAGEREF _Toc498862015 \h 70Table 16. Stepwise multiple regression analysis between pre-cold FF%, age, sex and body fat percentage PAGEREF _Toc498862016 \h 72Table 17. Stepwise multiple regression analysis between pre-cold T2*, age, sex and body fat percentage PAGEREF _Toc498862017 \h 73Table 18. Stepwise multiple regression analysis between FF% reduction, age, sex and body fat percentage PAGEREF _Toc498862018 \h 74Table 19. Participant Demographics (Objective 3) PAGEREF _Toc498862019 \h 86Table 20. Simple regression analysis between liver fat content and its covariates PAGEREF _Toc498862020 \h 88Table 21. Relationship between liver fat with age and sex PAGEREF _Toc498862021 \h 89Table 22. Stepwise multiple regression analysis between liver fat, age, sex, pre-cold FF% and body fat percentage PAGEREF _Toc498862022 \h 90Table 23. Stepwise multiple regression analysis between liver fat content, age, sex, pre-cold T2* and % body fat. PAGEREF _Toc498862023 \h 91Table 24. Stepwise multiple regression analysis between liver fat, age, sex, FF% reduction and % body fat. PAGEREF _Toc498862024 \h 93List of Abbreviations18F-FDG: 18-fluorodeoxyglucoseATP: adenosine triphosphate BAT: brown adipose tissueBMI: body mass indexBOLD: blood-oxygen-level dependent CSI: chemical-shift imagingDEXA: dual energy x-ray absorptiometry DNL: de novo lipogenesis EMG: electromyography FF: fat-fraction GET-BAT: Gene Environment Team on Brown/Beige Adipose TissueHDL-C: high-density lipoprotein cholesterolICC: intra-class correlation coefficientISMRM: International Society for Magnetic Resonance in Medicine IRT: infrared thermography KO: knockoutLoA: limits of agreement MRI: magnetic resonance imagingMRS: magnetic resonance spectroscopyMST: mean skin temperature MUMC: McMaster University Medical Centre Myf5: myogenic factor 5NAFLD: non-alcoholic fatty liver diseaseNASH: non-alcoholic steatohepatitisOGTT: oral glucose tolerance testPax7: paired box protein Pax-7 PDFF: proton-density fat-fraction PET-CT: positron emission tomography – computer tomographyROI: region of interest RPAT: retroperitoneal adipose tissue SAT: subcutaneous adipose tissueSCV: supraclavicular fossaSJHH: St. Joseph Healthcare Hamilton SPV: subjects per variable T: tesla T2*: T2* relaxation T2D: type 2 diabetesTG: triglycerides Tph1: tryptophan hydroxylase 1 TRL: triglyceride-rich lipoprotein UCP1: uncoupling protein-1VAT: visceral adipose tissueVLDL: very low density lipoprotein WAT: white adipose tissueLITERATURE REVIEWBrown Adipose TissueBackgroundBrown adipose tissue (BAT) is a key site for non-shivering thermogenesis, which is defined as heat production not associated with muscle activity (i.e. shivering). It is present in small mammals living in cold environments and animals that undergo hibernation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/physrev.00015.2003", "ISBN" : "0031-9333 (Print) 0031-9333 (Linking)", "ISSN" : "0031-9333", "PMID" : "14715917", "abstract" : "The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.", "author" : [ { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiological Reviews", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "277-359", "title" : "Brown Adipose Tissue: Function and Physiological Significance", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴", "plainTextFormattedCitation" : "4", "previouslyFormattedCitation" : "⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4. These animals use the heat produced by BAT to warm their core body temperature. In humans, BAT functions as an important thermoregulator for infants and recently, imaging studies have shown that BAT is present in amounts significant enough to have an effect on metabolism in adult humans ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1056/NEJMoa0808949", "ISBN" : "1533-4406 (Electronic)\\r0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357407", "abstract" : "Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lidell", "given" : "Martin E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heglind", "given" : "Mikael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westergren", "given" : "Rickard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niemi", "given" : "Tarja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taittonen", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laine", "given" : "Jukka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savisto", "given" : "Nina-Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-3", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1518-1525", "title" : "Functional Brown Adipose Tissue in Healthy Adults", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1096/fj.09-133546", "ISBN" : "1530-6860 (Electronic)\\r0892-6638 (Linking)", "ISSN" : "0892-6638", "PMID" : "19417078", "abstract" : "Classically, adult humans have been considered not to possess active brown adipose tissue (BAT). However, positron-emission-tomography has shown fluorodeoxyglucose uptake that is distributed in such a way (e.g., in the neck) that it would seem to be BAT. Until now this has not been supported by direct evidence that these areas truly represented BAT, that is, the presence of the BAT-unique uncoupling protein-1 (UCP1). Samples of adipose tissue from the neck of 35 patients undergoing surgery for thyroid diseases were obtained and analyzed. In 1/3 of the subjects (the younger and leaner), distinct islands composed of UCP1 immunoreactive brown adipocytes could clearly be discerned, accounting for up to 1/3 of all adipocytes. The brown-adipose islands were richly sympathetically innervated (indicating acute central control); adjacent white adipose areas were not. The capillary density was high, implying a high capacity for oxygen delivery. Cells with features of brown adipocyte precursors were found in pericapillary areas. These data demonstrate that human adults indeed possess BAT and thus imply possibilities of future therapeutic strategies for the treatment of obesity, including maintenance of brown adipocytes and stimulation of the growth of preexisting brown precursors.", "author" : [ { "dropping-particle" : "", "family" : "Zingaretti", "given" : "M. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crosta", "given" : "F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guerrieri", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frontini", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedergaard", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cinti", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The FASEB Journal", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2009", "9", "1" ] ] }, "page" : "3113-3120", "title" : "The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^5\u20138", "plainTextFormattedCitation" : "5\u20138", "previouslyFormattedCitation" : "^5\u20138" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5–8.LocationBAT is strategically located around major blood vessels to ensure adequate delivery of substrates and effective dissipation of heat throughout the body. Infants and children have considerable amounts of active BAT which gradually regresses with age, especially after puberty ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MOL.0b013e3283425243", "ISBN" : "1476-5497 (Electronic)\\r0307-0565 (Linking)", "ISSN" : "0957-9672", "PMID" : "21157334", "abstract" : "Human brown adipose tissue (BAT) has recently found to be functionally active in adults. The purpose of this review is to chart the importance of BAT in the light of recent publications in humans.", "author" : [ { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Lipidology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "2" ] ] }, "page" : "49-54", "title" : "Brown adipose tissue in humans", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹", "plainTextFormattedCitation" : "9", "previouslyFormattedCitation" : "⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }9. In infants, BAT constitutes 1 to 5% of their body weight and is largely found in the interscapular region ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0300-5127", "PMID" : "1001650", "author" : [ { "dropping-particle" : "", "family" : "Hull", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochemical Society Transactions", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1976" ] ] }, "page" : "226-228", "title" : "The function of brown adipose tissue in the newborn", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10. In children and adults, BAT is found mainly in the supraclavicular fossa (SCV) and in the mediastinal, thoracic paravertebral, perinephric, and adrenal regions (see Figure 1) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^11\u201313", "plainTextFormattedCitation" : "11\u201313", "previouslyFormattedCitation" : "^11\u201313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11–13.Known sites of BAT activation in adult humans according to 18-fluorodeoxyglucose (18F-FDG) uptake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "¹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13. Origin and Development BAT forms before other fat depots during embryonic development and consists of a homogeneous population of adipocytes. BAT originates from precursor cells that also give rise to skeletal muscle cells ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.3361", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "24100998", "abstract" : "Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.", "author" : [ { "dropping-particle" : "", "family" : "Harms", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seale", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10", "29" ] ] }, "page" : "1252-1263", "publisher" : "Nature Publishing Group", "title" : "Brown and beige fat: development, function and therapeutic potential", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "¹⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14. These precursor cells express two particular genes, myogenic factor 5 (Myf5) and paired box protein Pax-7 (Pax7), which are selective markers of cells in the mesoderm that develop into skeletal myogenic cells. However, it is not known whether these Myf5 expressing cells are either multipotent or consist of separate pools of Myf5 cells that give rise to muscle cells, brown or white adipocytes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.3361", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "24100998", "abstract" : "Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.", "author" : [ { "dropping-particle" : "", "family" : "Harms", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seale", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10", "29" ] ] }, "page" : "1252-1263", "publisher" : "Nature Publishing Group", "title" : "Brown and beige fat: development, function and therapeutic potential", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "¹⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14.MorphologyBAT has morphological characteristics that differ from white adipose tissue (WAT). BAT contains a central nucleus, multiple lipid droplets and has an abundance of iron-rich mitochondria. These mitochondria are unique in that their inner membranes contain uncoupling protein-1 (UCP1) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00183.2009", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "19458063", "abstract" : "Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ associates with resistance to obesity and related disorders. Another example of physiological transdifferetiation of adipocytes is offered by the mammary gland; the pregnancy hormonal stimuli seems to trigger a reversible transdifferentiation of adipocytes into milk-secreting epithelial glands. The obese adipose organ is infiltrated by macrophages inducing chronic inflamation that is widely considered as a causative factor for insulin resistance. We showed that the vast majority of macrophages infiltrating the obese organ are arranged around dead adipocytes, forming characteristic crown-like structures. We recently found that visceral fat is more infiltrated than the subcutaneous fat despite a smaller size of visceral adipocytes. This suggests a different susceptibility of visceral and subcutaneous adipocytes to death, raising the concept of smaller critical death size that could be important to explain the key role of visceral fat for the metabolic disorders associated with obesity.", "author" : [ { "dropping-particle" : "", "family" : "Cinti", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "977-986", "title" : "Transdifferentiation properties of adipocytes in the adipose organ", "type" : "article-journal", "volume" : "297" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "¹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15. When activated, this specific protein uncouples and bypasses the electron transport chain responsible for adenosine triphosphate (ATP) synthesis producing heat ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/physrev.00015.2003", "ISBN" : "0031-9333 (Print) 0031-9333 (Linking)", "ISSN" : "0031-9333", "PMID" : "14715917", "abstract" : "The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.", "author" : [ { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiological Reviews", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "277-359", "title" : "Brown Adipose Tissue: Function and Physiological Significance", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴", "plainTextFormattedCitation" : "4", "previouslyFormattedCitation" : "⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4. In addition, BAT is highly vascularized and densely innervated by terminal fibres of the sympathetic nervous system ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "¹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13. In comparison, WAT consists of a unilocular lipid droplet, a displaced peripheral nucleus, and limited cytoplasm ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "¹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16. Recently, cells with thermogenic potential and morphologic features similar to BAT have also been identified. Most commonly termed as beige adipose tissue, these cells express UCP1 in response to adrenergic stimuli and have function similar to classic brown adipocytes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.3361", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "24100998", "abstract" : "Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.", "author" : [ { "dropping-particle" : "", "family" : "Harms", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seale", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10", "29" ] ] }, "page" : "1252-1263", "publisher" : "Nature Publishing Group", "title" : "Brown and beige fat: development, function and therapeutic potential", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "¹⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14. Factors associated with BATMost of the studies that have assessed factors associated with BAT were conducted using 18F-FDG Positron Emission Tomography – Computer Tomography (PET-CT). In these studies, they established negative associations between BAT (volume and activity) and adiposity as well as age while the relationship between BAT outcomes with sex and outdoor temperature are inconsistent, which may in part be due to inconsistent cold stimulation of BAT. BMI and Adiposity BAT metabolic activity is inversely related to body mass index (BMI) and adiposity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/db10-0004", "ISBN" : "1939-327X (Electronic)\\n0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "20357363", "abstract" : "OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.\\n\\nRESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.\\n\\nRESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09).\\n\\nCONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.", "author" : [ { "dropping-particle" : "", "family" : "Pfannenberg", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Matthias K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripkens", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stef", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deckert", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmadl", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimold", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "Hans Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claussen", "given" : "Claus D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefan", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7", "1" ] ] }, "page" : "1789-1793", "title" : "Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/oby.2010.105", "ISBN" : "1930-7381 (Print) 1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "20448535", "abstract" : "Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20\u201328 years underwent FDG-PET after 2-h cold exposure at 19 \u00b0C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 \u00b0C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 \u00b1 97 kcal/day, being comparable with that of the BAT-negative group (1,434 \u00b1 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 \u00b1 293 (P < 0.05) and slightly by 42 \u00b1 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 \u00b0C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 \u00b0C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "6" ] ] }, "page" : "13-16", "publisher" : "Nature Publishing Group", "title" : "Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/oby.20456", "ISBN" : "1930-739X (Electronic)\\r1930-7381 (Linking)", "ISSN" : "19307381", "PMID" : "23554353", "abstract" : "OBJECTIVE: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. DESIGN AND METHODS: Using positron emission tomography (PET), we quantified cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans. Further, cold-induced glucose uptake was measured in obese subjects before and after a five-month conventional weight loss. RESULTS: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. CONCLUSIONS: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.", "author" : [ { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noponen", "given" : "Tommi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viljanen", "given" : "Tapio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-6", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2279-2287", "title" : "Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1056/NEJMoa0808718", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357405", "abstract" : "Background Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. Methods We studied 24 healthy men \u2014 10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], <25) and 14 who were overweight or obese (BMI, \u226525) \u2014 under thermoneutral conditions (22\u00b0C) and during mild cold exposure (16\u00b0C). Putative brown-adipose-tissue activity was ...", "author" : [ { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanhommerig", "given" : "Joost W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smulders", "given" : "Nanda M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossaerts", "given" : "Jamie M.A.F.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemerink", "given" : "Gerrit J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouvy", "given" : "Nicole D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teule", "given" : "G.J. Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-7", "issue" : "15", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1500-1508", "title" : "Cold-Activated Brown Adipose Tissue in Healthy Men", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.2967/jnumed.112.117275", "ISBN" : "1535-5667", "ISSN" : "1535-5667", "PMID" : "23868958", "abstract" : "UNLABELLED:The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging.\\n\\nMETHODS:BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge.\\n\\nRESULTS:Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% \u00b1 1.8% (P < 0.01).\\n\\nCONCLUSION:We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Yin-Ching Iris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yih-Chieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwong", "given" : "Kenneth K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "id" : "ITEM-9", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "1584-1587", "publisher" : "Society of Nuclear Medicine", "title" : "Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{5,6,11,17\u201322}", "plainTextFormattedCitation" : "5,6,11,17\u201322", "previouslyFormattedCitation" : "^{5,6,11,17\u201322}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,6,11,17–22 in adult humans. Saito et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶", "plainTextFormattedCitation" : "6", "previouslyFormattedCitation" : "⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6 exposed 56 healthy adult volunteers to an intermittent cold exposure using ice blocks (every 5 minutes for a duration of approximately 4 minutes) in an air-conditioned room (19°C for two hours). They found 18F-FDG uptake was inversely related to BMI (r = -0.67), total body fat (r = -0.56) and visceral fat (r = -0.68). Similar results were found in 24 healthy men subjected to 16°C cold treatment in a climate chamber for two hours. BAT metabolic activity was negatively correlated with both BMI (r = -0.60) and percent body fat (r = -0.60) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0808718", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357405", "abstract" : "Background Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. Methods We studied 24 healthy men \u2014 10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], <25) and 14 who were overweight or obese (BMI, \u226525) \u2014 under thermoneutral conditions (22\u00b0C) and during mild cold exposure (16\u00b0C). Putative brown-adipose-tissue activity was ...", "author" : [ { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanhommerig", "given" : "Joost W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smulders", "given" : "Nanda M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossaerts", "given" : "Jamie M.A.F.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemerink", "given" : "Gerrit J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouvy", "given" : "Nicole D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teule", "given" : "G.J. Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1500-1508", "title" : "Cold-Activated Brown Adipose Tissue in Healthy Men", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "²¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21. These findings provide strong supporting data that BAT activity is closely related to measures of adiposity in adults. Age A review by Ponrartana and colleagues ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/nyas.12195", "ISBN" : "1749-6632", "ISSN" : "00778923", "PMID" : "23909713", "abstract" : "The visualization of brown adipose tissue (BAT) in pediatric patients undergoing positron emission tomography/computed tomography (PET/CT) examinations is dependent on multiple physiologic and technical factors, such as age, sexual maturity, fat accumulation, disease status, medications, plasma glucose concentration, radiotracer dosage, acquisition parameters, and season and temperature during examinations. Evidence also suggests that children with metabolically active BAT have significantly greater muscle volume than those without visualized BAT, and that in both boys and girls, the amount of BAT increases during puberty. Hence, concurrent with the gains in skeletal muscle during infancy and puberty, all infants and adolescents have large amounts of BAT. New magnetic resonance imaging (MRI) techniques that discern the cytological differences between brown and white adipose tissue will likely provide the platform to reliably measure BAT in healthy subjects and determine the relevance of this tissue in humans.", "author" : [ { "dropping-particle" : "", "family" : "Ponrartana", "given" : "Skorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "24-29", "title" : "On the relevance of brown adipose tissue in children", "type" : "article-journal", "volume" : "1302" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³", "plainTextFormattedCitation" : "23", "previouslyFormattedCitation" : "²³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }23 concluded that BAT prevalence is ten times higher in children than in adults. In adults, age also has an impact as shown by Yoneshiro and colleagues. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2011.125", "ISBN" : "1930-7381 (Print)\\r1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "21566561", "abstract" : "Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 \u00b0C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-Ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "9", "12" ] ] }, "page" : "1755-1760", "publisher" : "Nature Publishing Group", "title" : "Age-Related Decrease in Cold-Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴", "plainTextFormattedCitation" : "24", "previouslyFormattedCitation" : "²⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }24 BAT was identified in half of the participants in their twenties but less than 10% in their fifties and none in their sixties after a brief cold exposure. These results are also consistent with other studies that reported an inverse relationship between BAT and age ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/oby.2010.105", "ISBN" : "1930-7381 (Print) 1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "20448535", "abstract" : "Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20\u201328 years underwent FDG-PET after 2-h cold exposure at 19 \u00b0C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 \u00b0C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 \u00b1 97 kcal/day, being comparable with that of the BAT-negative group (1,434 \u00b1 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 \u00b1 293 (P < 0.05) and slightly by 42 \u00b1 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 \u00b0C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 \u00b0C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "6" ] ] }, "page" : "13-16", "publisher" : "Nature Publishing Group", "title" : "Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.2967/jnumed.112.117275", "ISBN" : "1535-5667", "ISSN" : "1535-5667", "PMID" : "23868958", "abstract" : "UNLABELLED:The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging.\\n\\nMETHODS:BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge.\\n\\nRESULTS:Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% \u00b1 1.8% (P < 0.01).\\n\\nCONCLUSION:We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Yin-Ching Iris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yih-Chieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwong", "given" : "Kenneth K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "id" : "ITEM-6", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "1584-1587", "publisher" : "Society of Nuclear Medicine", "title" : "Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/oby.20456", "ISBN" : "1930-739X (Electronic)\\r1930-7381 (Linking)", "ISSN" : "19307381", "PMID" : "23554353", "abstract" : "OBJECTIVE: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. DESIGN AND METHODS: Using positron emission tomography (PET), we quantified cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans. Further, cold-induced glucose uptake was measured in obese subjects before and after a five-month conventional weight loss. RESULTS: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. CONCLUSIONS: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.", "author" : [ { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noponen", "given" : "Tommi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viljanen", "given" : "Tapio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-7", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2279-2287", "title" : "Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{5,6,11,18\u201320,22}", "plainTextFormattedCitation" : "5,6,11,18\u201320,22", "previouslyFormattedCitation" : "^{5,6,11,18\u201320,22}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,6,11,18–20,22.SexThere are conflicting results in the literature regarding the relationship between BAT and sex. In studies conducted retrospectively, BAT prevalence was higher in females than males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db10-0004", "ISBN" : "1939-327X (Electronic)\\n0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "20357363", "abstract" : "OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.\\n\\nRESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.\\n\\nRESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09).\\n\\nCONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.", "author" : [ { "dropping-particle" : "", "family" : "Pfannenberg", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Matthias K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripkens", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stef", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deckert", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmadl", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimold", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "Hans Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claussen", "given" : "Claus D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefan", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7", "1" ] ] }, "page" : "1789-1793", "title" : "Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^5,17", "plainTextFormattedCitation" : "5,17", "previouslyFormattedCitation" : "^5,17" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,17. However, these results might be inaccurate since on average, females tend to feel colder at a higher temperature compared to males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸", "plainTextFormattedCitation" : "18", "previouslyFormattedCitation" : "¹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }18. These retrospectives studies might, therefore, be biased by the inherently lower temperatures in hospitals which could be sufficient in activating BAT in females but not in males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpregu.00021.2014", "ISBN" : "1522-1490 (Electronic)\\r0363-6119 (Linking)", "ISSN" : "0363-6119", "PMID" : "24871967", "abstract" : "The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the \u201cfixed volume\u201d methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "A. A. J. J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierts", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "W. D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Regulatory, Integrative and Comparative Physiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "103-113", "title" : "Cold-activated brown adipose tissue in human adults: methodological issues", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "²⁵" }, "properties" : { "noteIndex" : 24 }, "schema" : "" }25. In contrast to these findings, cold-activated BAT studies have shown that BAT prevalence is similar in both males and females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI68993", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738", "PMID" : "23867626", "abstract" : "In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show \"browning\" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "Anouk A J J", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeks", "given" : "Joris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "Boudewijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vijgen", "given" : "Guy H E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visser", "given" : "Mari\u00eblle G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "Maarten J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f6rgensen", "given" : "Johanna A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottaghy", "given" : "Felix M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Investigation", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8", "1" ] ] }, "page" : "3395-3403", "title" : "Cold acclimation recruits human brown fat and increases nonshivering thermogenesis", "type" : "article-journal", "volume" : "123" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1073/pnas.1207911109", "ISBN" : "0027-8424", "ISSN" : "0027-8424", "PMID" : "22665804", "abstract" : "As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "A. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Y.-C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sze", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "English", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holman", "given" : "A. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "M. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "G. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences", "id" : "ITEM-2", "issue" : "25", "issued" : { "date-parts" : [ [ "2012", "6", "19" ] ] }, "page" : "10001-10005", "publisher" : "National Academy of Sciences", "title" : "Cold but not sympathomimetics activates human brown adipose tissue in vivo", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^26,27", "plainTextFormattedCitation" : "26,27", "previouslyFormattedCitation" : "^26,27" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26,27. Outdoor temperature In several retrospective studies, BAT metabolic activity has been shown to be inversely related to outdoor temperature ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-2", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^5,11,18", "plainTextFormattedCitation" : "5,11,18", "previouslyFormattedCitation" : "^5,11,18" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,11,18. These groups found that BAT is more likely to be detected in studies conducted on days with lower outdoor temperature. Similarly, Saito and colleagues ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶", "plainTextFormattedCitation" : "6", "previouslyFormattedCitation" : "⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6 reported higher BAT prevalence in participants that were enrolled in the winter than in the summer. Given the retrospective nature of these studies, BAT measurements did not include either an acclimatization period or a cold treatment to stimulate BAT activity. Recently, Haq et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/s41598-017-11537-x", "ISSN" : "2045-2322", "abstract" : "The discovery of brown adipose tissue (BAT) in adults has sparked interest in its role as a therapeutic target in metabolic disorders. Infrared thermography is a promising way to quantify BAT; however, a standardized methodology has not been established. This study aims to establish a standardized and reproducible protocol to measure thermal response to cold in the supraclavicular area using thermographic imaging. In Phase 1, we compared the thermal response to 12 \u00b0C cold after acclimation at either 32 \u00b0C or room temperature using thermographic imaging. Repeatability of the 32 \u00b0C acclimation trial was studied in a second group in Phase 2. Phase 1 included 28 men (mean age 23.9 \u00b1 5.9 y; mean BMI 25.2 \u00b1 3.9 kg/m2) and Phase 2 included 14 men (mean age 20.9 \u00b1 2.4 y; mean BMI 23.6 \u00b1 3.1 kg/m2). The thermal response was greater after 32 \u00b0C than after room temperature acclimation (0.22 \u00b1 0.19 vs 0.13 \u00b1 0.17 \u00b0C, p = 0.05), was not related to outdoor temperature (r = \u22120.35, p = 0.07), did not correlate with supraclavicular fat (r = \u22120.26, p = 0.21) measured with dual-energy x-ray absorptiometry and was repeatable [ICC 0.69 (0.14\u20130.72)]. Acclimation at 32 \u00b0C followed by cold generates a reproducible change in supraclavicular skin temperature measurable by thermal imaging that may be indicative of BAT metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Haq", "given" : "Tahniyah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crane", "given" : "Justin D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanji", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gunn", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinberg", "given" : "Gregory R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scientific Reports", "id" : "ITEM-1", "issue" : "11934", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "publisher" : "Springer US", "title" : "Optimizing the methodology for measuring supraclavicular skin temperature using infrared thermography; implications for measuring brown adipose tissue activity in humans", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁸", "plainTextFormattedCitation" : "28", "previouslyFormattedCitation" : "²⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28 showed the importance of an acclimatization phase where following an acclimation period of one hour at either room temperature or at 32°C prior to the cold exposure, BAT activity in response to cold stimulation (as measured by infrared thermography) was not related to outdoor temperature. IMAGING MODALITIES TO DETECT BATAs a potential therapeutic target, it is important to develop accurate, precise, robust and reproducible non-invasive modalities to measure BAT. To date, imaging modalities have been most widely utilized to detect BAT including the use of 18F-FDG PET-CT and MRI. 18F-FDG PET-CT18F-FDG PET-CT is the most widely used measure of BAT volume and metabolic activity. Histology studies have confirmed the presence of BAT in SCV tissue with increased 18F-FDG uptake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-0530", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "19401428", "abstract" : "OBJECTIVE The significant roles of brown adipose tissue (BAT) in the regulation of energy expenditure and adiposity are established in small rodents but have been controversial in humans. The objective is to examine the prevalence of metabolically active BAT in healthy adult humans and to clarify the effects of cold exposure and adiposity. RESEARCH DESIGN AND METHODS In vivo 2-[(18)F]fluoro-2-deoxyglucose (FDG) uptake into adipose tissue was measured in 56 healthy volunteers (31 male and 25 female subjects) aged 23-65 years by positron emission tomography (PET) combined with X-ray computed tomography (CT). RESULTS When exposed to cold (19 degrees C) for 2 h, 17 of 32 younger subjects (aged 23-35 years) and 2 of 24 elderly subjects (aged 38-65 years) showed a substantial FDG uptake into adipose tissue of the supraclavicular and paraspinal regions, whereas they showed no detectable uptake when kept warm (27 degrees C). Histological examinations confirmed the presence of brown adipocytes in these regions. The cold-activated FDG uptake was increased in winter compared with summer (P < 0.001) and was inversely related to BMI (P < 0.001) and total (P < 0.01) and visceral (P < 0.001) fat areas estimated from CT image at the umbilical level. CONCLUSIONS Our findings, being against the conventional view, indicate the high incidence of metabolically active BAT in adult humans and suggest a role in the control of body temperature and adiposity.", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-Ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-Kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2009", "7", "1" ] ] }, "page" : "1526-1531", "title" : "High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1056/NEJMoa0808949", "ISBN" : "1533-4406 (Electronic)\\r0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357407", "abstract" : "Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lidell", "given" : "Martin E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heglind", "given" : "Mikael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westergren", "given" : "Rickard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niemi", "given" : "Tarja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taittonen", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laine", "given" : "Jukka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savisto", "given" : "Nina-Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-2", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1518-1525", "title" : "Functional Brown Adipose Tissue in Healthy Adults", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^7,29", "plainTextFormattedCitation" : "7,29", "previouslyFormattedCitation" : "^7,29" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7,29. 18F-FDG PET-CT scans measure the uptake of a glucose analogue that is taken up by brown adipocytes but is not metabolized, thus remaining trapped in the adipocyte. The combination of PET with CT allows anatomical localization of the 18F-FDG uptake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "¹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13. Although 18F-FDG PET-CT has been considered the gold standard, a complete picture of BAT metabolism and morphology is not provided by this imaging as this method relies on the amount of glucose that is being taken up by BAT during activation. It is now known that the primary and initial substrate for non-shivering thermogenesis are endogenously derived fatty acids followed by circulating fatty acids ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1139/y86-101", "ISBN" : "0030229505338", "ISSN" : "0008-4212", "PMID" : "3730946", "abstract" : "The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 mumol/min) and release of glycerol (0.9 and 1.2 mumol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 mumol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation.(ABSTRACT TRUNCATED AT 250 WORDS)", "author" : [ { "dropping-particle" : "", "family" : "Ma", "given" : "Stephanie W. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foster", "given" : "David O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian Journal of Physiology and Pharmacology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1986", "5" ] ] }, "page" : "609-614", "title" : "Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue <i>in vivo</i>", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1152/physrev.00015.2003", "ISBN" : "0031-9333 (Print) 0031-9333 (Linking)", "ISSN" : "0031-9333", "PMID" : "14715917", "abstract" : "The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.", "author" : [ { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiological Reviews", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "277-359", "title" : "Brown Adipose Tissue: Function and Physiological Significance", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^4,30,31", "plainTextFormattedCitation" : "4,30,31", "previouslyFormattedCitation" : "^4,30,31" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4,30,31. Therefore, relying on glucose uptake as a measure of BAT as is done in 18F-FDG PET-CT leads to the underestimation of BAT mass and metabolic activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "³¹", "plainTextFormattedCitation" : "31", "previouslyFormattedCitation" : "³¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31. In addition, 18F-FDG PET-CT is unable to detect inactive or weakly activated BAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-0530", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "19401428", "abstract" : "OBJECTIVE The significant roles of brown adipose tissue (BAT) in the regulation of energy expenditure and adiposity are established in small rodents but have been controversial in humans. The objective is to examine the prevalence of metabolically active BAT in healthy adult humans and to clarify the effects of cold exposure and adiposity. RESEARCH DESIGN AND METHODS In vivo 2-[(18)F]fluoro-2-deoxyglucose (FDG) uptake into adipose tissue was measured in 56 healthy volunteers (31 male and 25 female subjects) aged 23-65 years by positron emission tomography (PET) combined with X-ray computed tomography (CT). RESULTS When exposed to cold (19 degrees C) for 2 h, 17 of 32 younger subjects (aged 23-35 years) and 2 of 24 elderly subjects (aged 38-65 years) showed a substantial FDG uptake into adipose tissue of the supraclavicular and paraspinal regions, whereas they showed no detectable uptake when kept warm (27 degrees C). Histological examinations confirmed the presence of brown adipocytes in these regions. The cold-activated FDG uptake was increased in winter compared with summer (P < 0.001) and was inversely related to BMI (P < 0.001) and total (P < 0.01) and visceral (P < 0.001) fat areas estimated from CT image at the umbilical level. CONCLUSIONS Our findings, being against the conventional view, indicate the high incidence of metabolically active BAT in adult humans and suggest a role in the control of body temperature and adiposity.", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-Ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-Kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2009", "7", "1" ] ] }, "page" : "1526-1531", "title" : "High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1056/NEJMoa0808718", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357405", "abstract" : "Background Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. Methods We studied 24 healthy men \u2014 10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], <25) and 14 who were overweight or obese (BMI, \u226525) \u2014 under thermoneutral conditions (22\u00b0C) and during mild cold exposure (16\u00b0C). Putative brown-adipose-tissue activity was ...", "author" : [ { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanhommerig", "given" : "Joost W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smulders", "given" : "Nanda M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossaerts", "given" : "Jamie M.A.F.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemerink", "given" : "Gerrit J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouvy", "given" : "Nicole D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teule", "given" : "G.J. Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-2", "issue" : "15", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1500-1508", "title" : "Cold-Activated Brown Adipose Tissue in Healthy Men", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^21,29", "plainTextFormattedCitation" : "21,29", "previouslyFormattedCitation" : "^21,29" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21,29. Confirming these concerns is a recent study in which 18F-FDG uptake persisted in UCP-1 knockout (KO) mice (therefore without active BAT); thereby dissociating BAT thermogenesis and 18FDG uptake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.116.186460", "ISBN" : "4934197133", "ISSN" : "0161-5505", "PMID" : "28082439", "abstract" : "(18)F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain whether BAT (18)F-FDG uptake reliably tracks UCP1-mediated heat production. METHODS UCP1 knockout (UCP1 KO) and wild-type mice received the selective \u03b23 adrenergic receptor agonist CL 316, 243 (1mg/kg) and underwent metabolic cage, infrared thermal imaging and (18)F-FDG PET/magnetic resonance imaging (MRI) experiments. Primary brown adipocytes were additionally examined for their bioenergetics as well as their uptake of 2-deoxy-3H-glucose. RESULTS In response to CL 316, 243 treatments, oxygen consumption and BAT thermogenesis were diminished in UCP1 KO mice but BAT (18)F-FDG uptake was fully retained. UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected. CONCLUSION Increased BAT (18)F-FDG uptake can occur independently of UCP1 function.", "author" : [ { "dropping-particle" : "", "family" : "Hankir", "given" : "Mohammed K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kranz", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keipert", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiner", "given" : "Juliane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andreasen", "given" : "Sille G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patt", "given" : "Marianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kl\u00f6ting", "given" : "Nora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiker", "given" : "John T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brust", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hesse", "given" : "Swen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jastroch", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fenske", "given" : "Wiebke K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1100-1103", "title" : "Dissociation Between Brown Adipose Tissue ¹⁸ F-FDG Uptake and Thermogenesis in Uncoupling Protein 1\u2013Deficient Mice", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³²", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32. PET-CT also involves significant radiation exposure and therefore cannot be used for large-scale studies in healthy individuals or in vulnerable populations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2014.07.025", "ISBN" : "2122633255", "ISSN" : "19327420", "PMID" : "25185947", "abstract" : "As part of a current worldwide effort to understand the physiology of human BAT (hBAT) and whether its thermogenic activity can be manipulated to treat obesity, the workshop \"Exploring the Roles of Brown Fat in Humans\" was convened at the National Institutes of Health on February 25-26, 2014. Presentations and discussion indicated that hBAT and its physiological roles are highly complex, and research is needed to understand the health impact of hBAT beyond thermogenesis and body weight regulation, and to define its interactions with core physiological processes like glucose homeostasis, cachexia, physical activity, bone structure, sleep, and circadian rhythms. \u00a9 2014 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haft", "given" : "Carol R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laughlin", "given" : "Maren R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "9" ] ] }, "page" : "408-415", "title" : "Brown fat in humans: Consensus points and experimental guidelines", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³³", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "³³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }33. It is also expensive, time-consuming and, in the absence of a cold stimulation, has extremely low reproducibility ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11. MRIGiven the limitations of 18F-FDG PET-CT in measuring BAT, other modalities to quantify BAT are now being evaluated, including the use of MRI. BAT MR Characteristics The intrinsic morphologic differences between BAT and WAT result in unique magnetic resonance signatures that can be detected by MRI in the form of proton-density fat-fraction (PDFF) and T2* relaxation (T2*) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35. PDFF is a fundamental property of tissue that accurately reflects the concentration of fat in tissue. It is defined as the ratio of triglycerides (TG) to the sum of TG and water. At the 2012 meeting of the International Society for Magnetic Resonance in Medicine (ISMRM), PDFF was recommended as the standardized imaging biomarker of tissue fat content because of its accuracy, precision, robustness, and reproducibility ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.23741", "ISBN" : "6314442508", "ISSN" : "10531807", "PMID" : "25792328", "abstract" : "On February 19\u201322, the 2012 ISMRM Workshop on Fat\u2013Water Separation was held in Long Beach, California. Over 130 attendees from 13 countries convened to discuss historical aspects of water\u2013fat imaging, as well as technical and clinical developments, and remaining challenges. Among these attendees were new and established investigators. A comprehensive overview of the meeting and presentations from the 25 invited speakers at the workshop was recently published in Magnetic Resonance in Medicine (1). As illustrated in Figure 1 below, scientific interest in fat quantification using MR spectroscopy (MRS) and MR imaging (MRI) has grown steadily in the past decade. Accordingly, many of the invited lectures and scientific abstracts at the meeting focused on emerging MRS-and MRI-based methods to quantify tissue fat concentration. Applications included quantification of tissue fat concentration in organs and tissues such as liver, pancreas, skeletal muscle, heart, thymus, bone marrow, and white and brown adipose tissue, as well as the use of MRI techniques to quantify and characterize fat content for the food industry. During these lectures and ensuing discussions, a theme that emerged multiple times was the need to standardize MR-based biomarkers for assessing tissue fat concentration. While many different MR-based biomarkers may be considered for fat quantification, an informal consensus was reached at the meeting that proton-density fat-fraction (PDFF) is currently the most practical and meaningful MR-based biomarker for this purpose. Thus, the goal of this editorial is to provide a formal statement from three of the organizers of the ISMRM workshop on the choice of PDFF as the standardized MR-based biomarker for tissue fat concentration.", "author" : [ { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sirlin", "given" : "Claude B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "11" ] ] }, "page" : "1011-1014", "publisher" : "Wiley Subscription Services, Inc., A Wiley Company", "title" : "Proton density fat-fraction: A standardized mr-based biomarker of tissue fat concentration", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁶", "plainTextFormattedCitation" : "36", "previouslyFormattedCitation" : "³⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }36. It has been shown to be insensitive to changes in acquisition parameters, scanner manufacturer, imaging centre and field strength. Brown adipocytes are known to have lower lipid content and higher water content in comparison to white adipocytes resulting in a lower FF value ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,37,38", "plainTextFormattedCitation" : "16,37,38", "previouslyFormattedCitation" : "^16,37,38" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,37,38. T2* is defined as the decay of transverse magnetization mainly caused by magnetic field inhomogeneity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/rg.295095034", "ISBN" : "1527-1323 (Electronic)\\r0271-5333 (Linking)", "ISSN" : "0271-5333", "PMID" : "19755604", "abstract" : "T2* relaxation refers to decay of transverse magnetization caused by a combination of spin-spin relaxation and magnetic field inhomogeneity. T2* relaxation is seen only with gradient-echo (GRE) imaging because transverse relaxation caused by magnetic field inhomogeneities is eliminated by the 180 degrees pulse at spin-echo imaging. T2* relaxation is one of the main determinants of image contrast with GRE sequences and forms the basis for many magnetic resonance (MR) applications, such as susceptibility-weighted (SW) imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be made predominantly T2* weighted by using a low flip angle, long echo time, and long repetition time. GRE sequences with T2*-based contrast are used to depict hemorrhage, calcification, and iron deposition in various tissues and lesions. SW imaging uses phase information in addition to T2*-based contrast to exploit the magnetic susceptibility differences of the blood and of iron and calcification in various tissues. Perfusion MR imaging exploits the signal intensity decrease that occurs with the passage of a high concentration of gadopentetate dimeglumine through the microvasculature. Change in oxygen saturation during specific tasks changes the local T2*, which leads to the blood oxygen level-dependent effect seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted sequences, and their clinical applications are presented, followed by the principles, techniques, and clinical uses of four T2*-based applications, including SW imaging, perfusion MR imaging, functional MR imaging, and iron overload imaging", "author" : [ { "dropping-particle" : "", "family" : "Chavhan", "given" : "Govind B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babyn", "given" : "Paul S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Bejoy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shroff", "given" : "Manohar M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haacke", "given" : "E. Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RadioGraphics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1433-1449", "publisher" : "Radiological Society of North America", "title" : "Principles, Techniques, and Applications of T2*-based MR Imaging and Its Special Applications", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁹", "plainTextFormattedCitation" : "39", "previouslyFormattedCitation" : "³⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39. The use of T2* to measure BAT primarily relies on the differences in magnetic susceptibility of various tissues in the body. The high abundance of iron-rich mitochondria in BAT in contrast to WAT causes a faster T2* relaxation, resulting in reduced T2* values ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/nbm.903", "ISBN" : "0952-3480", "ISSN" : "09523480", "PMID" : "15526352", "abstract" : "Ferritin, the iron storing protein, is known to darken T2-weighted MRI. This darkening can be used to non-invasively measure iron content. However, ferritin's behavior is not the same in tissue as in solution, a discrepancy that remains unexplained by the recently developed theory matching the NMR properties of ferritin solutions. A better understanding of the relaxation induced by ferritin in tissue could help for the development of new MRI protocols of iron quantification. In this short review, the main relaxation properties of ferritin in solution and in tissue are presented together with a discussion of the possible reasons for the faster transverse relaxation observed in tissues.", "author" : [ { "dropping-particle" : "", "family" : "Gossuin", "given" : "Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller", "given" : "Robert N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillis", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2004", "11" ] ] }, "page" : "427-432", "publisher" : "John Wiley & Sons, Ltd.", "title" : "Relaxation induced by ferritin: A better understanding for an improved MRI iron quantification", "type" : "article", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1148/rg.295095034", "ISBN" : "1527-1323 (Electronic)\\r0271-5333 (Linking)", "ISSN" : "0271-5333", "PMID" : "19755604", "abstract" : "T2* relaxation refers to decay of transverse magnetization caused by a combination of spin-spin relaxation and magnetic field inhomogeneity. T2* relaxation is seen only with gradient-echo (GRE) imaging because transverse relaxation caused by magnetic field inhomogeneities is eliminated by the 180 degrees pulse at spin-echo imaging. T2* relaxation is one of the main determinants of image contrast with GRE sequences and forms the basis for many magnetic resonance (MR) applications, such as susceptibility-weighted (SW) imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be made predominantly T2* weighted by using a low flip angle, long echo time, and long repetition time. GRE sequences with T2*-based contrast are used to depict hemorrhage, calcification, and iron deposition in various tissues and lesions. SW imaging uses phase information in addition to T2*-based contrast to exploit the magnetic susceptibility differences of the blood and of iron and calcification in various tissues. Perfusion MR imaging exploits the signal intensity decrease that occurs with the passage of a high concentration of gadopentetate dimeglumine through the microvasculature. Change in oxygen saturation during specific tasks changes the local T2*, which leads to the blood oxygen level-dependent effect seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted sequences, and their clinical applications are presented, followed by the principles, techniques, and clinical uses of four T2*-based applications, including SW imaging, perfusion MR imaging, functional MR imaging, and iron overload imaging", "author" : [ { "dropping-particle" : "", "family" : "Chavhan", "given" : "Govind B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babyn", "given" : "Paul S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Bejoy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shroff", "given" : "Manohar M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haacke", "given" : "E. Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RadioGraphics", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1433-1449", "publisher" : "Radiological Society of North America", "title" : "Principles, Techniques, and Applications of T2*-based MR Imaging and Its Special Applications", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^39,40", "plainTextFormattedCitation" : "39,40", "previouslyFormattedCitation" : "^39,40" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,40. BAT MR ActivityIn addition to MRI’s ability to differentiate BAT and WAT structurally, both FF and T2* may be used to measure BAT metabolic activity. BAT uses endogenous derived fatty acid when activated resulting in a decreased triglyceride content (i.e. lower FF value) upon BAT activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.109.068775", "ISBN" : "1535-5667 (Electronic) 0161-5505 (Linking)", "ISSN" : "0161-5505", "PMID" : "20124047", "abstract" : "Brown adipose tissue (BAT) densities assessed as CT Hounsfield units (HUs) were evaluated in a rodent model and in patients to determine whether HUs changed in relation to BAT activity. METHODS: Serial (18)F-FDG PET/CT was performed on rats under both room temperature control conditions and after 4 h of cold-stimulation, which is known to activate BAT. The maximum standardized uptake values and CT HUs of BAT were measured, and tissues were examined in the laboratory. Image records from cancer patients who underwent PET/CT were reviewed, and 23 patients were identified who displayed both high and low (18)F-FDG uptake into BAT on serial (18)F-FDG PET/CT scans. The maximum standardized uptake values and CT HUs of BAT were compared in these scans. RESULTS: The mean (+/-SD) CT HUs of cold-activated BAT (-12.4 +/- 22.4) were significantly higher than those (-27.9 +/- 9.6) of the controls in the rat model. The CT HUs of BAT (-71.6 +/- 18.0) in the patients with high (18)F-FDG uptake were significantly higher than those (-104.4 +/- 16.8) of the patients with low (18)F-FDG uptake . A decrease in relative lipid content is seen in activated BAT in rats on histology. CONCLUSION: The CT HUs of BAT increased in activated conditions in both animals and patients, likely because of lipid consumption by activated BAT.", "author" : [ { "dropping-particle" : "", "family" : "Baba", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacene", "given" : "H. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engles", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Honda", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahl", "given" : "R. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "246-250", "publisher" : "Society of Nuclear Medicine", "title" : "CT Hounsfield Units of Brown Adipose Tissue Increase with Activation: Preclinical and Clinical Studies", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^31,41", "plainTextFormattedCitation" : "31,41", "previouslyFormattedCitation" : "^31,41" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,41. This decline in FF% might be confounded by an increase in blood perfusion that occurs during BAT activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2011.06.012", "ISBN" : "1932-7420 (Electronic)\\r1550-4131 (Linking)", "ISSN" : "15504131", "PMID" : "21803297", "abstract" : "We investigated the metabolism of human brown adipose tissue (BAT) in healthy subjects by determining its cold-induced and insulin-stimulated glucose uptake and blood flow (perfusion) using positron emission tomography (PET) combined with computed tomography (CT). Second, we assessed gene expression in human BAT and white adipose tissue (WAT). Glucose uptake was induced 12-fold in BAT by cold, accompanied by doubling of perfusion. We found a positive association between whole-body energy expenditure and BAT perfusion. Insulin enhanced glucose uptake 5-fold in BAT independently of its perfusion, while the effect on WAT was weaker. The gene expression level of insulin-sensitive glucose transporter GLUT4 was also higher in BAT as compared to WAT. In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner. \u00a9 2011 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lidell", "given" : "Martin E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oikonen", "given" : "Vesa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noponen", "given" : "Tommi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viljanen", "given" : "Tapio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheinin", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taittonen", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niemi", "given" : "Tarja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "8", "3" ] ] }, "page" : "272-279", "title" : "Different metabolic responses of human brown adipose tissue to activation by cold and insulin", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2967/jnumed.112.111336", "ISBN" : "1535-5667 (Electronic)\\n0161-5505 (Linking)", "ISSN" : "0161-5505", "PMID" : "23362317", "abstract" : "UNLABELLED Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog (18)F-FDG has shown unequivocally the existence of functional BAT in adult humans, suggesting that many humans retain some functional BAT past infancy. The objective of this study was to determine to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and (18)F-FDG tracer uptake. METHODS Twenty-five healthy adults (15 women and 10 men; mean age \u00b1 SD, 30 \u00b1 7 y) underwent triple-oxygen scans (H2(15)O, C(15)O, and (15)O2) as well as measurements of daily energy expenditure (DEE; kcal/d) both at rest and after exposure to mild cold (15.5\u00b0C [60\u00b0F]) using indirect calorimetry. The subjects were divided into 2 groups (high BAT and low BAT) based on the presence or absence of (18)F-FDG tracer uptake (standardized uptake value [SUV] > 2) in cervical-supraclavicular BAT. Blood flow and oxygen extraction fraction (OEF) were calculated from dynamic PET scans at the location of BAT, muscle, and white adipose tissue. Regional blood oxygen saturation was determined by near-infrared spectroscopy. The total energy expenditure during rest and mild cold stress was measured by indirect calorimetry. Tissue-level metabolic rate of oxygen (MRO2) in BAT was determined and used to calculate the contribution of activated BAT to DEE. RESULTS The mass of activated BAT was 59.1 \u00b1 17.5 g (range, 32-85 g) in the high-BAT group (8 women and 1 man; mean age, 29.6 \u00b1 5.5 y) and 2.2 \u00b1 3.6 g (range, 0-9.3 g) in the low-BAT group (9 men and 7 women; mean age, 31.4 \u00b1 10 y). Corresponding maximal SUVs were significantly higher in the high-BAT group than in the low-BAT group (10.7 \u00b1 3.9 vs. 2.1 \u00b1 0.7, P = 0.01). Blood flow values were significantly higher in the high-BAT group than in the low-BAT group for BAT (12.9 \u00b1 4.1 vs. 5.9 \u00b1 2.2 mL/100 g/min, P = 0.03) and white adipose tissue (7.2 \u00b1 3.4 vs. 5.7 \u00b1 2.3 mL/100 g/min, P = 0.03) but were similar for muscle (4.4 \u00b1 1.9 vs. 3.9 \u00b1 1.7 mL/100 g/min). Moreover, OEF in BAT was similar in the 2 groups (0.51 \u00b1 0.17 in high-BAT group vs. 0.47 \u00b1 0.18 in low-BAT group, P = 0.39). During mild cold stress, calculated MRO2 values in BAT increased from 0.97 \u00b1 0.53 to 1.42 \u00b1 0.68 mL/100 g/min (P = 0.04) in the high-BAT group and were significantly higher than those determined in the low-BAT group (0.40\u2026", "author" : [ { "dropping-particle" : "", "family" : "Muzik", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangner", "given" : "T. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leonard", "given" : "W. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janisse", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Granneman", "given" : "J. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "4", "1" ] ] }, "page" : "523-531", "publisher" : "Society of Nuclear Medicine", "title" : "15O PET Measurement of Blood Flow and Oxygen Consumption in Cold-Activated Human Brown Fat", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2967/jnumed.109.068775", "ISBN" : "1535-5667 (Electronic) 0161-5505 (Linking)", "ISSN" : "0161-5505", "PMID" : "20124047", "abstract" : "Brown adipose tissue (BAT) densities assessed as CT Hounsfield units (HUs) were evaluated in a rodent model and in patients to determine whether HUs changed in relation to BAT activity. METHODS: Serial (18)F-FDG PET/CT was performed on rats under both room temperature control conditions and after 4 h of cold-stimulation, which is known to activate BAT. The maximum standardized uptake values and CT HUs of BAT were measured, and tissues were examined in the laboratory. Image records from cancer patients who underwent PET/CT were reviewed, and 23 patients were identified who displayed both high and low (18)F-FDG uptake into BAT on serial (18)F-FDG PET/CT scans. The maximum standardized uptake values and CT HUs of BAT were compared in these scans. RESULTS: The mean (+/-SD) CT HUs of cold-activated BAT (-12.4 +/- 22.4) were significantly higher than those (-27.9 +/- 9.6) of the controls in the rat model. The CT HUs of BAT (-71.6 +/- 18.0) in the patients with high (18)F-FDG uptake were significantly higher than those (-104.4 +/- 16.8) of the patients with low (18)F-FDG uptake . A decrease in relative lipid content is seen in activated BAT in rats on histology. CONCLUSION: The CT HUs of BAT increased in activated conditions in both animals and patients, likely because of lipid consumption by activated BAT.", "author" : [ { "dropping-particle" : "", "family" : "Baba", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacene", "given" : "H. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engles", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Honda", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahl", "given" : "R. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "246-250", "publisher" : "Society of Nuclear Medicine", "title" : "CT Hounsfield Units of Brown Adipose Tissue Increase with Activation: Preclinical and Clinical Studies", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^41\u201343", "plainTextFormattedCitation" : "41\u201343", "previouslyFormattedCitation" : "^41\u201343" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }41–43. However, a recent study showed that blood perfusion has minimal effects on the MR FF signal, as changes in FF% were negligible after a brief warm exposure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁴", "plainTextFormattedCitation" : "44", "previouslyFormattedCitation" : "⁷⁷" }, "properties" : { "noteIndex" : 82 }, "schema" : "" }44.The use of T2* relaxation in measuring BAT activity is mainly dependent on the magnetic properties of haemoglobin. Haemoglobin can either be saturated with oxygen molecules (oxyhaemoglobin) or desaturated with oxygen molecules (deoxyhaemoglobin). Oxygen consumption is increased in regions with BAT activation resulting in a higher deoxyhaemoglobin concentration in BAT regions (i.e. lower T2* values) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/rg.295095034", "ISBN" : "1527-1323 (Electronic)\\r0271-5333 (Linking)", "ISSN" : "0271-5333", "PMID" : "19755604", "abstract" : "T2* relaxation refers to decay of transverse magnetization caused by a combination of spin-spin relaxation and magnetic field inhomogeneity. T2* relaxation is seen only with gradient-echo (GRE) imaging because transverse relaxation caused by magnetic field inhomogeneities is eliminated by the 180 degrees pulse at spin-echo imaging. T2* relaxation is one of the main determinants of image contrast with GRE sequences and forms the basis for many magnetic resonance (MR) applications, such as susceptibility-weighted (SW) imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be made predominantly T2* weighted by using a low flip angle, long echo time, and long repetition time. GRE sequences with T2*-based contrast are used to depict hemorrhage, calcification, and iron deposition in various tissues and lesions. SW imaging uses phase information in addition to T2*-based contrast to exploit the magnetic susceptibility differences of the blood and of iron and calcification in various tissues. Perfusion MR imaging exploits the signal intensity decrease that occurs with the passage of a high concentration of gadopentetate dimeglumine through the microvasculature. Change in oxygen saturation during specific tasks changes the local T2*, which leads to the blood oxygen level-dependent effect seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted sequences, and their clinical applications are presented, followed by the principles, techniques, and clinical uses of four T2*-based applications, including SW imaging, perfusion MR imaging, functional MR imaging, and iron overload imaging", "author" : [ { "dropping-particle" : "", "family" : "Chavhan", "given" : "Govind B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babyn", "given" : "Paul S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Bejoy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shroff", "given" : "Manohar M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haacke", "given" : "E. Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RadioGraphics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1433-1449", "publisher" : "Radiological Society of North America", "title" : "Principles, Techniques, and Applications of T2*-based MR Imaging and Its Special Applications", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁹", "plainTextFormattedCitation" : "39", "previouslyFormattedCitation" : "³⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39. Non-Alcoholic Fatty Liver Disease BackgroundNon-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases caused by an excessive accumulation of fat in the liver in the absence of other liver conditions and/or significant alcohol consumption. NAFLD is the most common liver disease worldwide – its prevalence is estimated to range from 25 to 45% and is closely linked with metabolic disorders such as obesity and type 2 diabetes (T2D) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cld.2015.01.012", "ISBN" : "9780323393409", "ISSN" : "15578224", "PMID" : "25921668", "abstract" : "Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies.", "author" : [ { "dropping-particle" : "", "family" : "Noureddin", "given" : "Mazen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinella", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinics in Liver Disease", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "361-379", "publisher" : "Elsevier Inc", "title" : "Nonalcoholic Fatty Liver Disease, Diabetes, Obesity, and Hepatocellular Carcinoma", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁵", "plainTextFormattedCitation" : "45", "previouslyFormattedCitation" : "⁴⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }45. The spectrum ranges from hepatic steatosis to non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis. There are many factors associated with NAFLD progression; among them are genetics, diet, metabolic and inflammatory factors as well as dysbiosis of gut microbiota ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/1751-2980.12291", "ISBN" : "1751-2972", "ISSN" : "17512972", "PMID" : "26406351", "abstract" : "Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide with a reported prevalence ranging from 6-33%, depending on the studied population. It encompasses a spectrum of liver manifestations ranging from simple steatosis (also known as nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NAFLD is strongly associated with components of the metabolic syndrome, mainly obesity and type 2 diabetes mellitus. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality. Current paradigm suggests a benign course for NAFL whereas NASH is considered to be the progressive phenotype. Although previously under-recognized accumulating evidence suggests that NAFL may also progress, suggesting a higher number of patients at risk than previously appreciated. Liver-biopsy remains the gold standard for definitive diagnosis, but the majority of patients can be diagnosed accurately by noninvasive methods. Approved therapies for NAFLD are still lacking and lifestyle modifications aiming at weight-loss remain the mainstay of NAFLD treatment. Intensive research could identify insulin resistance, lipotoxicity and dysbiosis of the gut microbiota as major pathophysiological mechanisms, leading to the development of promising targeted therapies which are currently investigated in clinical trials. In this review we summarize the current knowledge of NAFLD epidemiology, natural history, diagnosis, pathogenesis, and treatment and consider future directions. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Demir", "given" : "M\u00fcnevver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lang", "given" : "Sonja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steffen", "given" : "Hans-Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Digestive Diseases", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "541-557", "title" : "Nonalcoholic fatty liver disease - current status and future directions", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁶", "plainTextFormattedCitation" : "46", "previouslyFormattedCitation" : "⁴⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46. Although NAFLD is very common, a small proportion of patients with NAFLD develop NASH. NASH is defined by the presence of hepatic steatosis and evidence of hepatocyte damage; specifically the presence of inflammation and significant fibrosis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/hep.28431", "ISBN" : "0270-9139", "ISSN" : "15273350", "PMID" : "26707365", "abstract" : "BACKGROUND AND AIM: NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression and outcomes of NAFLD and NASH.\\n\\nMETHODS: Pubmed/MEDLINE were searched from 1989-2015 for terms involving epidemiology and progression of NAFLD.\\n\\nEXCLUSIONS: selected groups (only morbidly obese or diabetics or pediatric), no data on alcohol consumption or other liver diseases. Incidence of HCC, cirrhosis, overall mortality and liver-related mortality were determined. NASH required histologic criteria. All studies were reviewed by 3 independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication and study population. We used random-effects models to provide point estimates (95% CI) of prevalence, incidence, mortality and incidence rate ratios, and meta-regression with sub-group analysis to account for heterogeneity.\\n\\nRESULTS: Out of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (22.10-28.65) with highest prevalence in Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity [51.34% (41.38-61.20)], type 2 diabetes [22.51% (17.92-27.89)], hyperlipidemia [69.16% (49.91-83.46%)], hypertension [(39.34% (33.15-45.88)]] and metabolic syndrome [42.54% (30.06-56.05)] . Fibrosis progression proportion, measured in Brunt's score, and mean annual rate of progression in NASH were 40.76% (34.69-47.13) and 0.09 (0.06-0.12). HCC incidence among NAFLD patients was 0.44/1000 person-years (0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77/1000 person-years (0.33-1.77) and 11.77/1000 person-years (7.10-19.53), 15.44/1000 person-years (11.72-20.34) and 25.56/1000 person-years (6.29-103.80). Incidence Risk Ratios for liver-specific and overall mortality for NAFLD were 1.94 (1.28-2.92) and 1.05 (0.70-1.56).\\n\\nCONCLUSIONS: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous.f This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Younossi", "given" : "Zobair M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koenig", "given" : "Aaron B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdelatif", "given" : "Dinan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fazel", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henry", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wymer", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "73-84", "title" : "Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁷", "plainTextFormattedCitation" : "47", "previouslyFormattedCitation" : "⁴⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }47. Hepatic fibrosis is characterized by the accumulation of excessive connective tissue (scarring) in the liver caused by chronic liver cell injury. As fibrosis progresses, hepatic structure and function can be severely disrupted and may lead to liver cirrhosis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/hep.28431", "ISBN" : "0270-9139", "ISSN" : "15273350", "PMID" : "26707365", "abstract" : "BACKGROUND AND AIM: NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression and outcomes of NAFLD and NASH.\\n\\nMETHODS: Pubmed/MEDLINE were searched from 1989-2015 for terms involving epidemiology and progression of NAFLD.\\n\\nEXCLUSIONS: selected groups (only morbidly obese or diabetics or pediatric), no data on alcohol consumption or other liver diseases. Incidence of HCC, cirrhosis, overall mortality and liver-related mortality were determined. NASH required histologic criteria. All studies were reviewed by 3 independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication and study population. We used random-effects models to provide point estimates (95% CI) of prevalence, incidence, mortality and incidence rate ratios, and meta-regression with sub-group analysis to account for heterogeneity.\\n\\nRESULTS: Out of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (22.10-28.65) with highest prevalence in Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity [51.34% (41.38-61.20)], type 2 diabetes [22.51% (17.92-27.89)], hyperlipidemia [69.16% (49.91-83.46%)], hypertension [(39.34% (33.15-45.88)]] and metabolic syndrome [42.54% (30.06-56.05)] . Fibrosis progression proportion, measured in Brunt's score, and mean annual rate of progression in NASH were 40.76% (34.69-47.13) and 0.09 (0.06-0.12). HCC incidence among NAFLD patients was 0.44/1000 person-years (0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77/1000 person-years (0.33-1.77) and 11.77/1000 person-years (7.10-19.53), 15.44/1000 person-years (11.72-20.34) and 25.56/1000 person-years (6.29-103.80). Incidence Risk Ratios for liver-specific and overall mortality for NAFLD were 1.94 (1.28-2.92) and 1.05 (0.70-1.56).\\n\\nCONCLUSIONS: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous.f This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Younossi", "given" : "Zobair M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koenig", "given" : "Aaron B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdelatif", "given" : "Dinan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fazel", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henry", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wymer", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "73-84", "title" : "Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁷", "plainTextFormattedCitation" : "47", "previouslyFormattedCitation" : "⁴⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }47. Risk factors associated with NAFLD Given the potential for progression to more severe liver disease, it is important to understand the risk factors that predict the development of NAFLD, thereby facilitating early identification and potentially intervention. Obesity, metabolic syndrome, sex and genetic factors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cld.2015.01.012", "ISBN" : "9780323393409", "ISSN" : "15578224", "PMID" : "25921668", "abstract" : "Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies.", "author" : [ { "dropping-particle" : "", "family" : "Noureddin", "given" : "Mazen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinella", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinics in Liver Disease", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "361-379", "publisher" : "Elsevier Inc", "title" : "Nonalcoholic Fatty Liver Disease, Diabetes, Obesity, and Hepatocellular Carcinoma", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁵", "plainTextFormattedCitation" : "45", "previouslyFormattedCitation" : "⁴⁴" }, "properties" : { "noteIndex" : 18 }, "schema" : "" }45 are linked to NAFLD development. The following paragraphs will describe the known risk factors for NAFLD development.Obesity and Metabolic SyndromeThe prevalence of NAFLD is reported to be around 16% in normal weight individuals, but is higher in those with metabolic disorders and metabolic syndrome ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.atherosclerosis.2015.01.001", "ISBN" : "0021-9150", "ISSN" : "18791484", "PMID" : "25617860", "abstract" : "Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and the incidence of which is rising rapidly due to the increasing epidemic of obesity in both adults and children. The initial accumulation of fat followed by subsequent inflammation is central to the development of liver damage, and is critically influenced by host factors including age, gender, presence of diabetes, genetic polymorphisms and more recently by the gut microbiome. An increasing body of data suggest that NAFLD is also an independent risk factor of cardiovascular disease, which remains the commonest cause of mortality in such patients. This review focusses on the pathogenesis of NAFLD, and the evolution of new approaches to the management and treatment of NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Than", "given" : "Nwe Ni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newsome", "given" : "Philip N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Atherosclerosis", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "192-202", "publisher" : "Elsevier Ltd", "title" : "A concise review of non-alcoholic fatty liver disease", "type" : "article-journal", "volume" : "239" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁸", "plainTextFormattedCitation" : "48", "previouslyFormattedCitation" : "⁴⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }48. Metabolic syndrome, defined as a cluster of risk factors that increase a person’s risk of cardiovascular disease and type 2 diabetes (T2D) is defined by the presence of at least three of the following metabolic disorders: high blood pressure, high fasting glucose, increased triglyceride, low high-density lipoprotein cholesterol (HDL-C) and central obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/CIRCULATIONAHA.109.192644", "ISSN" : "00097322", "PMID" : "19805654", "abstract" : "A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.", "author" : [ { "dropping-particle" : "", "family" : "Alberti", "given" : "K. G M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckel", "given" : "Robert H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cleeman", "given" : "James I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donato", "given" : "Karen A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fruchart", "given" : "Jean Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "W. Philip T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loria", "given" : "Catherine M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Sidney C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "id" : "ITEM-1", "issue" : "16", "issued" : { "date-parts" : [ [ "2009", "10", "20" ] ] }, "page" : "1640-1645", "title" : "Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International ", "type" : "article-journal", "volume" : "120" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁹", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "⁴⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49. In a recent meta-analysis of 86 studies that included 8,515,431 participants from 22 countries, NAFLD was found in 51.34% with obesity, 22.51% with T2D, 69.16% with hyperlipidemia, 39.34% with hypertension and 42.54% with metabolic syndrome ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/hep.28431", "ISBN" : "0270-9139", "ISSN" : "15273350", "PMID" : "26707365", "abstract" : "BACKGROUND AND AIM: NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression and outcomes of NAFLD and NASH.\\n\\nMETHODS: Pubmed/MEDLINE were searched from 1989-2015 for terms involving epidemiology and progression of NAFLD.\\n\\nEXCLUSIONS: selected groups (only morbidly obese or diabetics or pediatric), no data on alcohol consumption or other liver diseases. Incidence of HCC, cirrhosis, overall mortality and liver-related mortality were determined. NASH required histologic criteria. All studies were reviewed by 3 independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication and study population. We used random-effects models to provide point estimates (95% CI) of prevalence, incidence, mortality and incidence rate ratios, and meta-regression with sub-group analysis to account for heterogeneity.\\n\\nRESULTS: Out of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (22.10-28.65) with highest prevalence in Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity [51.34% (41.38-61.20)], type 2 diabetes [22.51% (17.92-27.89)], hyperlipidemia [69.16% (49.91-83.46%)], hypertension [(39.34% (33.15-45.88)]] and metabolic syndrome [42.54% (30.06-56.05)] . Fibrosis progression proportion, measured in Brunt's score, and mean annual rate of progression in NASH were 40.76% (34.69-47.13) and 0.09 (0.06-0.12). HCC incidence among NAFLD patients was 0.44/1000 person-years (0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77/1000 person-years (0.33-1.77) and 11.77/1000 person-years (7.10-19.53), 15.44/1000 person-years (11.72-20.34) and 25.56/1000 person-years (6.29-103.80). Incidence Risk Ratios for liver-specific and overall mortality for NAFLD were 1.94 (1.28-2.92) and 1.05 (0.70-1.56).\\n\\nCONCLUSIONS: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous.f This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Younossi", "given" : "Zobair M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koenig", "given" : "Aaron B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdelatif", "given" : "Dinan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fazel", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henry", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wymer", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "73-84", "title" : "Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁷", "plainTextFormattedCitation" : "47", "previouslyFormattedCitation" : "⁴⁶" }, "properties" : { "noteIndex" : 18 }, "schema" : "" }47. These findings suggest that the development of NAFLD is closely linked to the presence of metabolic disorders. Sex The relationship between sex and NAFLD is currently unclear as there are conflicting results in the literature. In a study of 26,527 Asian subjects, the prevalence of NAFLD was higher in men (31%) than in women (16%) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1631/jzus.B0720016", "ISBN" : "1673-1581 1673-1581", "ISSN" : "1673-1581", "PMID" : "18763311", "abstract" : "OBJECTIVE: To investigate the relationship between alanine aminotransferase (ALT) levels and metabolic syndrome (MS) in nonalcoholic fatty liver disease (NAFLD).\\n\\nMETHODS: A total of 26527 subjects who received medical health checkup in our hospital from January 2005 to July 2007 were enrolled in the study. The diagnosis of fatty liver was based on ultrasound imaging. MS was defined according to the criteria of the Adult Treatment Panel III. ALT, triglyceride (TG), high density lipoprotein cholesterol (HDL-c), fasting plasma glucose (FPG), height, weight, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in each subject to analyze the relationship between MS and ALT activity.\\n\\nRESULTS: (1) The prevalence of NAFLD in men (30.94%) was significantly higher than that in women (15.65%); (2) The incidence of MS in NAFLD (33.83%) was significantly greater than that in non-NAFLD (10.62%); (3) Of the 6470 subjects with NAFLD, in the age-adjusted partial correlation analysis, there were statistically significant correlations between the ALT levels and most metabolic risk factors in each sex (P<0.01), except that ALT levels had no correlation with HDL-c in women. Moreover, in the multiple stepwise regression analysis, SBP lost its significance, and WC, body mass index (BMI), age, DBP, TG and FPG were independently associated with ALT levels in both sexes (P<0.05). HDL-c remained significant and was independently related to ALT levels in men; (4) ALT levels were significantly higher in subjects with MS compared to those without MS (P<0.001). Mean ALT levels increased with the number of MS components in each sex (P<0.05 for trend).\\n\\nCONCLUSION: We found a strong relationship between ALT levels and MS in NAFLD and revealed that the cluster of MS components might be the predictor for ALT elevations.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Zhou-wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Li-ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dai", "given" : "Hong-lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jian-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Li-zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Zhejiang University SCIENCE B", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "616-622", "title" : "Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁰", "plainTextFormattedCitation" : "50", "previouslyFormattedCitation" : "⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }50. Additionally, male gender was associated with elevated liver enzymes, NAFLD development as well as increased NAFLD-associated mortality ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.hepres.2005.09.007", "ISSN" : "13866346", "PMID" : "16203174", "abstract" : "AIMS The aim of our study was to elucidate the characteristics and natural history of Japanese nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS Two hundred and forty-seven patients were diagnosed as having biopsy-proven NAFLD at Tokyo Women's Medical University or an affiliated hospital from 1990 to June 2004. Biopsies were scored for the severity of steatosis, necro-inflammation, and fibrosis according to modified Brunt criteria. We assessed the clinicopathological features and natural history of NAFLD in patients stratified by the stage of their fibrosis. Univariate and multivariate logistic analyses were performed, and the diagnostic ability was assessed by the area under the receiver operating characteristic curve. RESULTS Clinicopathological features: The median age of the patients was 53 years, with a range from 10 to 89 years. There were 130 males and 117 females. Histologically, 46 patients were classified as F3 (bridging fibrosis), and 43 patients had F4 (cirrhosis). Females and older patients were more common in the F3-4 patients. Most of the F3-4 patients showed mild elevation of transaminases with significant deterioration of liver function tests compared with F0-2 patients. Ten patients were simultaneously diagnosed as having cirrhotic NASH and hepatocellular carcinoma (HCC). Natural history: During follow-up (median 44 months) of the F3-4 patients, 10 patients developed liver-related morbidity and five patients developed HCC. In the F3-4 patients, the 5-year cumulative incidence of HCC was 20%. Eight patients died (two of liver failure, four of HCC and two of other carcinomas). Serum markers for detecting F3-4: Serum hyaluronic acid levels can accurately evaluate NAFLD patients with F3-4. CONCLUSIONS The most important consequence of NAFLD patients with advanced fibrosis was HCC. Regular screening for this complication is extremely important.", "author" : [ { "dropping-particle" : "", "family" : "HASHIMOTO", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "YATSUJI", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "KANEDA", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "YOSHIOKA", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "TANIAI", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "TOKUSHIGE", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "SHIRATORI", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepatology Research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "72-76", "title" : "The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jhep.2008.06.018", "ISBN" : "0168-8278", "ISSN" : "01688278", "PMID" : "18682312", "abstract" : "Background/Aims: The natural history of non-alcoholic fatty liver disease (NAFLD) remains to be defined. We conducted a study to determine the overall and liver-related mortality of NAFLD in the general US population. Methods: In this study, the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES III-Linked Mortality File were used. Adjusted hazard ratios (HR) for overall and liver-related mortality were calculated for NAFLD using persons without liver disease as reference. Causes of death were determined. Results: After a median follow-up of 8.7 years, 80 persons with NAFLD and 1453 without liver disease died. Older age, male gender, non-Hispanic white race, lower educational level, lower income, higher BMI, presence of hypertension, diabetes mellitus, or metabolic syndrome were significantly (p < 0.05) associated with overall mortality. Persons with NAFLD had higher overall mortality [HR 1.038 (95% CI 1.036-1.041), P < 0.0001] and liver-related mortality [HR 9.32 (95% CI 9.21-9.43), P < 0.0001]. Liver disease was the third leading cause of death among persons with NAFLD after cardiovascular disease and malignancy. Conclusions: NAFLD is associated with higher overall and liver-related mortality in the general US population. Liver disease is a significant cause of death among persons with NAFLD. ?? 2008 European Association for the Study of the Liver.", "author" : [ { "dropping-particle" : "", "family" : "Ong", "given" : "Janus P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pitts", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Younossi", "given" : "Zobair M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Hepatology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "608-612", "title" : "Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/MEG.0b013e328011438b", "ISSN" : "0954-691X", "PMID" : "17353691", "abstract" : "OBJECTIVE Nonalcoholic fatty liver disease is an increasingly recognized condition, but its exact prevalence is unknown. In this prospective, multicenter study, we evaluated the prevalence of elevated alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl-transpeptidase levels as indirect markers of nonalcoholic fatty liver disease in volunteer blood donors as well as their associations with epidemiological and anthropometrical characteristics. METHODS Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transpeptidase levels were determined in blood donors from four transfusion centers during the morning sessions of a 3-month period. Cases with positive hepatitis B surface antigen, anti-hepatitis C virus, anti-HIV or elevated liver enzymes and alcohol abuse were excluded. RESULTS Abnormal liver enzymes were found in 17.6% of 3063 participants (alanine aminotransferase: 14.5%, aspartate aminotransferase: 4.6%, gamma-glutamyl-transpeptidase: 4.7%). Individuals with abnormal compared with those with normal liver enzymes or alanine aminotransferase values were more frequently men and had higher weight, body mass index, waist, hip and neck circumference (P<0.001 for all comparisons). The prevalence of abnormal liver enzymes was also associated with the transfusion center ranging between 8.8 and 22.1% (P<0.001) and alcohol consumption (P=0.001). In multivariate analysis, presence of elevated enzymes was independently associated with male sex, higher weight or body mass index, higher waist circumference and transfusion center. CONCLUSIONS More than 15% of Greek blood donors exhibit elevated liver enzymes, most likely as a result of unrecognized nonalcoholic fatty liver disease. The prevalence of nonalcoholic fatty liver disease is mainly associated with male sex, obesity and waist circumference, but it may range significantly among different population groups.", "author" : [ { "dropping-particle" : "V.", "family" : "Papatheodoridis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goulis", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christodoulou", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manolakopoulos", "given" : "Spilios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raptopoulou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrioti", "given" : "Evangelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexandropoulos", "given" : "Nikolaos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savvidou", "given" : "Savoula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papachristou", "given" : "Aikaterini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zervou", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seferiadis", "given" : "Kostas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kousidou", "given" : "Polyxeni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogiatzakis", "given" : "Evangelos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsianos", "given" : "Epaminondas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Gastroenterology & Hepatology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "page" : "281-287", "title" : "High prevalence of elevated liver enzymes in blood donors: associations with male gender and central adiposity", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^51\u201353", "plainTextFormattedCitation" : "51\u201353", "previouslyFormattedCitation" : "^50\u201352" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }51–53. However, a few studies have also reported that being a female conferred risks in developing NAFLD and fibrosis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.hepres.2005.09.007", "ISSN" : "13866346", "PMID" : "16203174", "abstract" : "AIMS The aim of our study was to elucidate the characteristics and natural history of Japanese nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS Two hundred and forty-seven patients were diagnosed as having biopsy-proven NAFLD at Tokyo Women's Medical University or an affiliated hospital from 1990 to June 2004. Biopsies were scored for the severity of steatosis, necro-inflammation, and fibrosis according to modified Brunt criteria. We assessed the clinicopathological features and natural history of NAFLD in patients stratified by the stage of their fibrosis. Univariate and multivariate logistic analyses were performed, and the diagnostic ability was assessed by the area under the receiver operating characteristic curve. RESULTS Clinicopathological features: The median age of the patients was 53 years, with a range from 10 to 89 years. There were 130 males and 117 females. Histologically, 46 patients were classified as F3 (bridging fibrosis), and 43 patients had F4 (cirrhosis). Females and older patients were more common in the F3-4 patients. Most of the F3-4 patients showed mild elevation of transaminases with significant deterioration of liver function tests compared with F0-2 patients. Ten patients were simultaneously diagnosed as having cirrhotic NASH and hepatocellular carcinoma (HCC). Natural history: During follow-up (median 44 months) of the F3-4 patients, 10 patients developed liver-related morbidity and five patients developed HCC. In the F3-4 patients, the 5-year cumulative incidence of HCC was 20%. Eight patients died (two of liver failure, four of HCC and two of other carcinomas). Serum markers for detecting F3-4: Serum hyaluronic acid levels can accurately evaluate NAFLD patients with F3-4. CONCLUSIONS The most important consequence of NAFLD patients with advanced fibrosis was HCC. Regular screening for this complication is extremely important.", "author" : [ { "dropping-particle" : "", "family" : "HASHIMOTO", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "YATSUJI", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "KANEDA", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "YOSHIOKA", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "TANIAI", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "TOKUSHIGE", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "SHIRATORI", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepatology Research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "72-76", "title" : "The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1381/0960892053576820", "ISSN" : "09608923", "PMID" : "15826462", "abstract" : "BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease in the United States. It is commonly associated with the components of the metabolic syndrome including obesity. From the spectrum of NAFLD, only patients with nonalcoholic steatohepatitis (NASH) have been convincingly shown to have a potential for progression to cirrhosis. We report the prevalence of NAFLD and NASH as well as predictors of NASH and advanced fibrosis in morbidly obese patients. METHODS 212 consecutive patients who underwent bariatric surgery were enrolled in the study. A liver biopsy was performed at the time of the surgery. Causes of chronic liver disease other than NAFLD were excluded by clinical and laboratory evaluation. RESULTS The prevalence of NAFLD was 93%. Of those with NAFLD, 26% had NASH. 17 patients (9%) had advanced fibrosis (i.e., bridging fibrosis or cirrhosis). Male gender, AST, and type 2 diabetes mellitus were independently associated with NASH. Waistto-hip ratio, AST, and focal hepatocyte necrosis on liver biopsy were independently associated with advanced fibrosis. Interestingly, while AST was associated with NASH and advanced fibrosis, the majority of the patients with either NASH or advanced fibrosis had normal AST. CONCLUSIONS NAFLD and NASH are very common in morbidly obese patients undergoing bariatric surgery. Features associated with the metabolic syndrome and liver cell injury are independently associated with either NASH or advanced fibrosis.", "author" : [ { "dropping-particle" : "", "family" : "Ong", "given" : "Janus P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elariny", "given" : "Hazem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collantes", "given" : "Rochelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Younoszai", "given" : "Abraham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandhoke", "given" : "Vikas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reines", "given" : "H. David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodman", "given" : "Zachary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Younossi", "given" : "Zobair M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity Surgery", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3", "1" ] ] }, "page" : "310-315", "title" : "Predictors of Nonalcoholic Steatohepatitis and Advanced Fibrosis in Morbidly Obese Patients", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^51,54", "plainTextFormattedCitation" : "51,54", "previouslyFormattedCitation" : "^50,53" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }51,54. It has been suggested that these discrepancies in the literature were most likely caused by either a sex difference in NAFLD pathogenesis or an inaccurate cut-off of liver enzymes in the diagnosis of NAFLD in females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04724.x", "ISBN" : "0269-2813\\r1365-2036", "ISSN" : "02692813", "PMID" : "21623852", "abstract" : "BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. AIM:To review epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. METHODS:An in-depth search of PubMed (1980-2010) was based on five search terms: &apos;non-alcoholic fatty liver disease&apos; OR &apos;non-alcoholic steatohepatitis&apos; OR &apos;fatty liver&apos; OR &apos;steatosis&apos; AND &apos;incidence&apos; [MeSH Terms] OR &apos;prevalence&apos; [MeSH Terms] OR &apos;natural history&apos;. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content. RESULTS:Four study categories included NAFLD incidence, prevalence, risk factors and natural history. Studies related to NAFLD prevalence and incidence indicate that the diagnosis is heterogeneous and relies on a variety of assessment tools, including liver biopsy, radiological tests such as ultrasonography, and blood testing such as liver enzymes. The prevalence of NAFLD is highest in populations with pre-existing metabolic conditions such as obesity and type II diabetes. Many studies investigating the natural history of NAFLD verify the progression from NASH to advanced fibrosis and hepatocellular carcinoma. CONCLUSIONS:Non-alcoholic fatty liver disease is the most common cause of elevated liver enzymes. Within the NAFLD spectrum, only NASH progresses to cirrhosis and hepatocellular carcinoma. With the growing epidemic of obesity, the prevalence and impact of NAFLD continues to increase, making NASH potentially the most common cause of advanced liver disease in coming decades.", "author" : [ { "dropping-particle" : "", "family" : "Vernon", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baranova", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Younossi", "given" : "Z. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology and Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "274-285", "title" : "Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁵", "plainTextFormattedCitation" : "55", "previouslyFormattedCitation" : "⁵⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }55. Race and Genetic FactorsIn a study of 567 patients, NAFLD prevalence was found to be different between races. Researchers in this study reported that NAFLD prevalence was highest in Hispanics (39%) followed by Caucasians (28%) and lowest in African Americans (12%) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10620-008-0234-x", "ISBN" : "0163-2116 (Print)\\n0163-2116 (Linking)", "ISSN" : "01632116", "PMID" : "18347982", "abstract" : "Nonalcoholic fatty liver disease (NAFLD) is a growing problem that is associated with the metabolic syndrome. The goal of the present study was to evaluate for ethnic differences in NAFLD and clinical correlates of NAFLD. The study population consisted of 567 patients seen at an urban obesity clinic. Elevated aminotransferase levels were used as a surrogate marker for NAFLD. The prevalence of elevated aminotransferases was highest in Hispanics (39%), followed by Caucasians (28%), and African Americans (12%). In univariate analysis, elevated aminotransferase levels were associated with ethnicity (Hispanic > African American, P < 0.001, and Caucasian > African American P = 0.030), hypertriglyceridemia (P < 0.001), and male gender (P < 0.001). The pattern of results was confirmed in multivariate analysis, except that the differences between Caucasians and African Americans was no longer significant. In conclusion, in an obesity clinic population, elevated aminotransferase levels and hypertriglyceridemia were most common in Hispanics and least common in African Americans.", "author" : [ { "dropping-particle" : "", "family" : "Kallwitz", "given" : "Eric R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Mrudula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Radhika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Reed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Layden-Almer", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cotler", "given" : "Scott J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestive Diseases and Sciences", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1358-1363", "title" : "Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: The impact of triglycerides", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁶", "plainTextFormattedCitation" : "56", "previouslyFormattedCitation" : "⁵⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }56. Genomic studies have shown that the allele PNPLA3-I148M is the most important genetic contributor to NAFLD development. Homozygous carriers of this allele have twice as much hepatic fat content as non-carriers. Homozygosity is most prevalent in Hispanics, the group most susceptible to NAFLD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.257", "ISBN" : "1546-1718 (Electronic)\\n1061-4036 (Linking)", "ISSN" : "1061-4036", "PMID" : "18820647", "abstract" : "Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9\u00d710(\u221210)) and with hepatic inflammation (P=3.7\u00d710(\u22124)). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Romeo", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozlitina", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Chao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pertsemlidis", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennacchio", "given" : "Len A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen", "given" : "Jonathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hobbs", "given" : "Helen H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Genetics", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1461-1465", "title" : "Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁷", "plainTextFormattedCitation" : "57", "previouslyFormattedCitation" : "⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }57. Another variant of the same gene called PNPLA3-S453I that is most common in African Americans but rare in European Americans and Hispanics has been associated with significantly lower liver fat content. These two allele variations were reported to account for 72% of the observed ethnic differences in hepatic fat content in a study cohort ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.257", "ISBN" : "1546-1718 (Electronic)\\n1061-4036 (Linking)", "ISSN" : "1061-4036", "PMID" : "18820647", "abstract" : "Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9\u00d710(\u221210)) and with hepatic inflammation (P=3.7\u00d710(\u22124)). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Romeo", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozlitina", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Chao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pertsemlidis", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennacchio", "given" : "Len A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen", "given" : "Jonathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hobbs", "given" : "Helen H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Genetics", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1461-1465", "title" : "Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁷", "plainTextFormattedCitation" : "57", "previouslyFormattedCitation" : "⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }57. These findings suggest race and genetic factors play a role in the development of NAFLD. Link between BAT and NafldThe association between BAT and NAFLD has not been extensively investigated. In two adult human studies conducted by the same research group, the investigators examined BAT and non-cold stimulated 18F-FDG PET-CT in a clinical sample (i.e. referred from oncology clinics) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59. Although they found that individuals with detectable BAT activity had lower NAFLD prevalence and better hepatic function than those without BAT activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59, the applicability of these findings to healthy humans remains uncertain.In rodent studies, increased BAT mass and metabolic activity have been shown to reverse or prevent the development of NAFLD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/cr.2013.64", "ISSN" : "1001-0602", "PMID" : "23649313", "abstract" : "\\nSupplementary information available for this article at ", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Xiaomeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Zongji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Xiaoming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Minghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Lan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Yanyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chi", "given" : "Qingsheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Dehua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Zhaoyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Chenzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yiming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xue", "given" : "Yaoming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Wanzhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Research", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "851-854", "title" : "Brown adipose tissue transplantation improves whole-body energy metabolism", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/en.2014-1598", "ISSN" : "19457170", "PMID" : "25830704", "abstract" : "Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased \u03b23-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. 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Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively. Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts \u03b2-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. 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However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased \u03b23-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. 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Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.", "author" : [ { "dropping-particle" : "", "family" : "Bartelt", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruns", "given" : "Oliver T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimer", "given" : "Rudolph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hohenberg", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ittrich", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peldschus", "given" : "Kersten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaul", "given" : "Michael G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tromsdorf", "given" : "Ulrich I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weller", "given" : "Horst", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waurisch", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eychm\u00fcller", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordts", "given" : "Philip L S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinninger", "given" : "Franz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruegelmann", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freund", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkel", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heeren", "given" : "Joerg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "200-205", "publisher" : "Nature Publishing Group", "title" : "Brown adipose tissue activity controls triglyceride clearance", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/en.2015-1092", "ISSN" : "19457170", "PMID" : "26372178", "abstract" : "High glucocorticoid concentrations are accompanied by metabolic side effects such as high plasma triglyceride (TG) concentrations. Liver, brown adipose tissue (BAT) and white adipose tissue are important regulators of plasma TG. Exposure to 4\u00b0C reduces plasma TG concentrations, and we therefore aimed to study the interaction between glucocorticoid excess and 24 hours of exposure to 4\u00b0C on lipid metabolism. For this, mice were implanted with 50-mg corticosterone or control pellets and housed for 24 hours at 23\u00b0C or 4\u00b0C 1 week later, after which various aspects of TG metabolism in liver, BAT, and white adipose tissue were studied. Corticosterone treatment resulted in a 3.8-fold increase of plasma TG concentrations. Increased TG was normalized by cold exposure, an effect still present 24 hours after cold exposure. Corticosterone treatment increased hepatic TG content by 3.5-fold and provoked secretion of large, TG-rich very low density lipoprotein particles. Cold exposure reduced very low density lipoprotein-TG secretion by approximately 50%. Corticosterone strongly decreased BAT activity: BAT weight increased by 3.5-fold, whereas uncoupling protein 1 (Ucp1) mRNA expression and Ucp1 protein content of BAT were reduced by 75% and 60%, respectively. Cold exposure partially normalized these parameters of BAT activity. The uptake of TG by BAT was not affected by corticosterone treatment but was increased 4.5-fold upon cold exposure. 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In another study, activation of BAT (via cold exposure) has been shown to attenuate corticosterone-induced hyperlipidemia by decreasing very low density lipoprotein (VLDL) production through reduced liver de novo lipogenesis (DNL) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/en.2015-1092", "ISSN" : "19457170", "PMID" : "26372178", "abstract" : "High glucocorticoid concentrations are accompanied by metabolic side effects such as high plasma triglyceride (TG) concentrations. Liver, brown adipose tissue (BAT) and white adipose tissue are important regulators of plasma TG. Exposure to 4\u00b0C reduces plasma TG concentrations, and we therefore aimed to study the interaction between glucocorticoid excess and 24 hours of exposure to 4\u00b0C on lipid metabolism. 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Thus, the association between BAT and liver fat may potentially be explained by the ability of BAT to clear substrate from circulation thereby shifting substrate clearance from liver to BAT depots. STUDY DESIGNRationaleThere has been renewed interest in the study of BAT as a potential therapeutic target for obesity, diabetes and NAFLD. There is now much evidence to suggest that BAT is not only important in thermogenesis but also plays an important role in metabolism ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db15-0146", "ISBN" : "0012-1797", "ISSN" : "1939327X", "PMID" : "26050667", "abstract" : "Brown adipose tissue (BAT) is a unique tissue that is able to convert chemical energy directly into heat when activated by the sympathetic nervous system. While initially believed to be of relevance only in human newborns and infants, research during recent years provided unequivocal evidence of active BAT in human adults. Moreover, it has become clear that BAT plays an important role in insulin sensitivity in rodents and humans. This has opened the possibility for exciting new therapies for obesity and diabetes. This review summarizes the current state of research with a special focus on recent advances regarding BAT and insulin resistance in human adults. 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In adults, cold-induced BAT activation has led to a significant increase in insulin sensitivity and energy expenditure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.3891", "ISBN" : "1546-170X", "ISSN" : "1078-8956", "PMID" : "26147760", "abstract" : "Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 \u00b0C) increased peripheral insulin sensitivity by \u223c43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, without effects on insulin signaling or AMP-activated protein kinase (AMPK) activation and only a minor increase in BAT glucose uptake.", "author" : [ { "dropping-particle" : "", "family" : "Hanssen", "given" : "Mark J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeks", "given" : "Joris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "Boudewijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lans", "given" : "Anouk A J J", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schaart", "given" : "Gert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Driessche", "given" : "Jos\u00e9 J", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f6rgensen", "given" : "Johanna A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Boekschoten", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hesselink", "given" : "Matthijs K C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Havekes", "given" : "Bas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kersten", "given" : "Sander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottaghy", "given" : "Felix M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "8", "6" ] ] }, "page" : "863-865", "title" : "Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db14-0746/-/DC1", "ISBN" : "4163612661", "ISSN" : "1939327X", "PMID" : "25056438", "abstract" : "Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.", "author" : [ { "dropping-particle" : "", "family" : "Chondronikola", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volpi", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f8rsheim", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porter", "given" : "Craig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Annamalai", "given" : "Palam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lidell", "given" : "Martin E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraf", "given" : "Manish K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labbe", "given" : "Sebastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hurren", "given" : "Nicholas M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yfanti", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chao", "given" : "Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Clark R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cesani", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawkins", "given" : "Hal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sidossis", "given" : "Labros S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "4089-4099", "title" : "Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^2,3", "plainTextFormattedCitation" : "2,3", "previouslyFormattedCitation" : "^2,3" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2,3 as well as decreased blood sugar levels ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db14-0746/-/DC1", "ISBN" : "4163612661", "ISSN" : "1939327X", "PMID" : "25056438", "abstract" : "Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.", "author" : [ { "dropping-particle" : "", "family" : "Chondronikola", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volpi", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f8rsheim", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porter", "given" : "Craig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Annamalai", "given" : "Palam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lidell", "given" : "Martin E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraf", "given" : "Manish K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labbe", "given" : "Sebastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hurren", "given" : "Nicholas M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yfanti", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chao", "given" : "Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Clark R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cesani", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawkins", "given" : "Hal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sidossis", "given" : "Labros S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "4089-4099", "title" : "Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³", "plainTextFormattedCitation" : "3", "previouslyFormattedCitation" : "³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }3. More recently, NAFLD was found to be inversely associated with BAT activity in mice lacking the enzyme, Tph1, a key enzyme in the synthesis of peripheral serotonin. These Tph1 KO mice had low levels of circulating serotonin, significantly higher BAT activity and were protected from NAFLD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.3766", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "25485911", "abstract" : "Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue, but its thermogenic potential is reduced with obesity and type 2 diabetes for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively. Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts \u03b2-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.", "author" : [ { "dropping-particle" : "", "family" : "Crane", "given" : "Justin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palanivel", "given" : "Rengasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottillo", "given" : "Emilio P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bujak", "given" : "Adam L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Huaqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ford", "given" : "Rebecca J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bl\u00fcmer", "given" : "Regje M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fullerton", "given" : "Morgan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yabut", "given" : "Julian M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Janice J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghia", "given" : "Jean-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamza", "given" : "Shereen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schertzer", "given" : "Jonathan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dyck", "given" : "Jason R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Waliul I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinberg", "given" : "Gregory R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2", "8" ] ] }, "page" : "166-172", "title" : "Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶²", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "⁶¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62. This study suggests that peripheral serotonin has a direct inhibitory effect on BAT thermogenesis in mice. Reducing this “brake” on BAT activity resulted in increased BAT activity and reduced hepatic steatosis was also identified. In humans, the relationship between BAT and NAFLD remains underexamined. In two retrospective 18F-FDG PET-CT studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59, BAT activity was inversely correlated with NAFLD prevalence in a study of 1832 participants ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁸", "plainTextFormattedCitation" : "58", "previouslyFormattedCitation" : "⁵⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58. Similarly, the presence of BAT in individuals was associated with better hepatic function and lower NAFLD prevalence ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁹", "plainTextFormattedCitation" : "59", "previouslyFormattedCitation" : "⁵⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }59. To date, imaging modalities have most widely been used to detect BAT including the use of 18F-FDG PET-CT and MRI. However, given the limitations associated with 18F-FDG PET-CT in measuring BAT, as described in Chapter 1, it is important to evaluate the use of other modalities to quantify BAT including the use of MRI.Significance Obesity is a chronic and progressive condition characterized by excess body fat. In Canada, one in four adults and one in 10 children are considered obese. This means that six million Canadians are currently living with obesity. Obesity increases the likelihood of various diseases such as atherosclerotic heart disease, type 2 diabetes, certain types of cancer and NAFLD. NAFLD is the most common cause of chronic liver disease worldwide. Currently, there are no pharmacological treatments for NAFLD. Therefore, it is important to identify factors that might be associated with hepatic fat accumulation such as the presence and activity of BAT to better understand if and how BAT can be targeted to treat NAFLD. ObjectivesProject Objectives: Develop and assess protocols for the use of MRI in measuring BAT characteristics and activity Examine the relationship between BAT (characteristics and activity) and known covariates such as age, sex, body fat percentage and outdoor temperature in adult humansDetermine if there is any association between BAT (characteristics and activity) and liver fat content in adult humans, before and after adjusting for potential covariates of liver fat such as age, sex and body fat percentage GET-BAT Study MethodologyTo address the three objectives for this thesis, a subset of data from the adult cohort of the Gene Environment Team on Brown/Beige Adipose Tissue (GET-BAT) study at McMaster University will be utilized. This ongoing cross-sectional study was designed to examine the inter-relationships between BAT, liver fat and the serotonin pathway in human children and adults. An outline of the adult arm of the GETBAT study is presented here, but the specific methods relevant to my thesis will be presented in the respective chapters.Inclusion / Exclusion CriteriaThis study was intended to include all adults age 18 to 50 years of age who agreed to the study protocol and did not have any of the exclusion criteria noted below. (Note that the initial age range of 18 to 60 years was later reduced to 18 to 50 years old because of difficulties in recruiting participants over 50 who were eligible for the study and due to the expected low incidence of BAT activity in those 50 years old and over ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2011.125", "ISBN" : "1930-7381 (Print)\\r1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "21566561", "abstract" : "Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 \u00b0C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-Ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "9", "12" ] ] }, "page" : "1755-1760", "publisher" : "Nature Publishing Group", "title" : "Age-Related Decrease in Cold-Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴", "plainTextFormattedCitation" : "24", "previouslyFormattedCitation" : "²⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }24). Self-reported alcohol intake ≥ 7 drinks/week and ≥ 3 drinks/day (males); ≥?2 drinks/day (females)Use of any of the following medications (β adrenergic, anti-hyperglycemic, antidepressant, anxiolytic, anti-psychotic, thyroid, 5HT3 antagonists, drugs known to influence brown adipocytes, serotonin and hepatic steatosis) – for a complete list of excluded medications, refer to Appendix Section 7.1.3; pp 107-111Tobacco and nicotine use (smoking, nicotine patch, chew tobacco, nicotine gum, e-cigarette or cigar)Any contraindications for MRI (claustrophobic, implanted metal, metallic injuries, recent tattoos and inability to fit inside the MR machine)Pregnant or nursingPrior bariatric surgery or liver transplantationAny conditions expected to be associated with brown adipose tissue dysfunction, hepatic steatosis or liver disorders – for a complete list of excluded conditions, refer to Appendix Section: 7.1.3; pp 112Subject Recruitment Participants were recruited in the McMaster and Hamilton community using posters, internal media advertising and social media postings. Recruitment locations included university and college campuses, churches, businesses, recreation and fitness centres, hospitals and primary care clinics. People who were interested in the study were first screened using our inclusion/exclusion list and the Imaging Research Centre’s screening form. Eligible participants were recruited for the study. Study VisitsThe study consisted of two visits. Visit 1 was held at McMaster University Medical Centre (MUMC) and visit 2 at St. Joseph Healthcare Hamilton (SJHH). Participants were reminded of their study visit four days (via email) and two days (via email and phone) before their visit date. In both visits, participants were asked to refrain from eating or drinking (with the exception of water) for at least 8 hours, vigorous physical activity for at least 48 hours, caffeine intake for at least 12 hours and serotonergic food (list included: banana, tomato, kiwi, walnut, avocado, pineapple and plum) for at least 24 hours before both Visits 1 and 2. Participants were also asked to shave any facial hair and to refrain from applying any type of facial or neck cream prior to visit 2. VISIT 1Participants were first consented to the study and were then re-screened for eligibility (initial screening was done during the recruitment phase). Anthropometrics (i.e. height, weight and waist circumference), blood pressure and body composition were then measured. Fasting bloodwork was collected and a 75 g oral glucose tolerance test (OGTT) was administered if the participant did not have known T2D (in which case only fasting blood sampling was conducted). VISIT 2 The visit started with participants acclimatizing to room temperature for at least 30 minutes before their initial MRI scan. After the initial MRI scan, 12 iButtons (wireless temperature loggers) were placed in different sites of the participants’ body to calculate a weighted mean skin temperature. Shivering intensity was also measured using electromyography (EMG) with sensors placed in the trapezius, vastus lateralis and vastus medialis. Participants were then exposed to a standardized cold exposure set at 18°C for 3 hours using a water-perfused suit. MRI scan was repeated immediately after the cold exposure. Booking Considerations for Female Participants The hormone estrogen promotes a lower body temperature (via vasodilation and heat dissipation) while progesterone has the opposite effect ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/cphy.c130029", "ISBN" : "2040-4603 (Electronic)\\r2040-4603 (Linking)", "ISSN" : "20404603", "PMID" : "24715568", "abstract" : "The present discussion reviews current knowledge regarding influences of the primary reproductive hormones on mechanisms of thermoregulatory control in women. The human body is remarkably capable of maintaining body temperature within a few tenths of a degree of normal (37\u00b0C) over a wide range of activity and environmental exposures; this regulation is accomplished via integration of central and peripheral thermal information at the preoptic area of the anterior hypothalamus (PO/AH). We describe both central and peripheral mechanisms involved in controlling thermoregulation in humans, and how these mechanisms are affected by sex and hormone exposure. Estrogens generally promote vasodilation, heat dissipation, and lower body temperature and progesterone or progestins generally have the opposite effect. Estrogens and progesterone/progestins can also interact with androgens; this is an important point because androgens in the body can increase in both older and younger women. The study of reproductive hormone (estrogens, progesterone, luteinizing, and follicle stimulating hormones) effects on body systems is challenging because of the complex and multifaceted influences of these hormones, both individually and in combination. Thus, a number of methods to alter hormone exposure are explained in this article. We conclude that men and women do not exhibit major quantitative differences in physiological thermoregulatory responses to exercise and/or body heating when factors such as fitness and body size are taken into account. However, female and male reproductive hormones have important influences that can significantly alter individual thermoregulatory responses at various points throughout the lifespan.", "author" : [ { "dropping-particle" : "", "family" : "Charkoudian", "given" : "Nisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stachenfeld", "given" : "Nina S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Comprehensive Physiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "3", "19" ] ] }, "page" : "793-804", "publisher" : "John Wiley & Sons, Inc.", "publisher-place" : "Hoboken, NJ, USA", "title" : "Reproductive hormone influences on thermoregulation in women", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁵", "plainTextFormattedCitation" : "65", "previouslyFormattedCitation" : "⁶⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }65.?Given fluctuations in estrogen and progesterone levels at various phases of the menstrual cycle, an attempt was made to standardize the timing of the visits relative to the menstrual cycle. Female participants were scheduled when their estrogen and progesterone levels were predicted to be at their lowest point which is generally within seven days of the start of menstruation. For females with regular menstruation and on oral contraceptives, participants were scheduled for their second visit within seven days following their next anticipated menstruation. For females with irregular menstruation, participants were asked to contact research personnel at the start of their next menstruation and the visit was booked within seven days.Visit TimelinesData presented in this thesis are from the shaded sections in Figures 2-3. * For a detailed list of study variables, refer to Appendix Section 7.1.1; pp 102-103.Visit 1 Timeline (McMaster University Medical Centre).Visit 2 Timeline (St. Joseph’s Healthcare Hamilton).Project RecruitmentRecruitment for the adult cohort started on July 2016. As of April 2017, 43 participants have been enrolled in the study, of which 41 have completed visit 1, 36 have completed visit 2 and 4 were ineligible after visit 1 (claustrophobic, thyroid medication, body size and copper IUD). The recruitment flow chart for the adult cohort is presented below in Figure 4. GET-BAT Adult Cohort Recruitment Flow Chart. The objectives of this thesis outlined previously in Section 2.3 will be discussed in the subsequent chapters. DevelopMENT AND ASSESSMENT OF MRI protocols IN MEASURING BAT characteristics and activity (OBJECTIVE 1) INTRODUCTIONThe first objective of this thesis focused on the development and assessment of protocols in using MRI to measure BAT characteristics and activity. The proof of concept MRI paper that showed BAT can be unequivocally identified in human infants has paved the way for new research in the development of MRI as a potential modality to detect BAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "¹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16. As an emerging field, MR techniques currently used to measure BAT in adult humans lack detailed methodology, standardization and consistency ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-8", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-9", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-10", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-11", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-12", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{37,38,66\u201374,44}", "plainTextFormattedCitation" : "37,38,66\u201374,44", "previouslyFormattedCitation" : "^{37,38,65\u201374}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38,66–74,44. Thus, it was important to develop a standardized protocol that could consistently and reliably measure BAT MR outcomes. To present these research questions more effectively, this chapter was separated into two sections. The first section highlights the steps undertaken in the development and design of an MRI protocol capable of measuring BAT characteristics and activity, while, the second section evaluated the effectiveness of the newly developed protocol in detecting BAT using MRI. DEVELOPMENT AND DESIGN OF PROTOCOL TO MEASURE BAT CHARACTERISTICS AND ACTIVITY USING MRIBACKGROUNDIn this section, the steps undertaken to develop a standardized protocol in detecting BAT using MRI technology are presented. Given that BAT activity is one of the primary outcomes in this study, a suitable cold exposure protocol that can consistently activate BAT had to be first defined. With the help of project collaborators at the University of Ottawa and Université de Sherbrooke, the research group was able to adapt the cold exposure protocol used at those sites to this study. This specific cooling protocol was previously shown to be adequate in stimulating BAT activity (as measured by PET-CT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ncomms14146", "ISSN" : "2041-1723", "PMID" : "28134339", "abstract" : "In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 \u00b0C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid ((18)FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Communications", "id" : "ITEM-2", "issue" : "14146", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "title" : "Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1113/jphysiol.2014.283598", "ISBN" : "0022-3751", "ISSN" : "1469-7793", "PMID" : "25384777", "abstract" : "KEY POINTS: Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering. Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men. Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized. ABSTRACT: Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold-defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U-(13) C]-palmitate and [3-(3) H]-glucose tracer methodologies coupled with positron emission tomography using (11) C-acetate and (18) F-fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold-induced increase in whole-body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 \u00b1 124 vs. 12 \u00b1 8 \u03bcmol min(-1) , respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WA\u2026", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "701-14", "title" : "Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men.", "type" : "article-journal", "volume" : "593" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2013-3901", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "19457197", "PMID" : "24423363", "abstract" : "Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild-cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes (T2D), which may have important pathological and therapeutic implications. Although, many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Objective: To determine whether four weeks of daily cold exposure could increase both the volume of metabolically active brown adipose tissue (BAT) and its oxidative capacity. Design: Six non-acclimated men were exposed to 10\u00b0C, two hours daily for four weeks (5 days/week), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with (11)C-acetate and (18)F-fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake and volume prior to and following four weeks of cold acclimation were examined under controlled acute cold exposure conditions. Results: The four-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66\u00b130 to 95\u00b128 mL, P<0.05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725\u00b10.300 to 1.591\u00b10.326 mL\u00b7sec(-1), P<0.05). Shivering intensity was not significantly different pre- compared to post-acclimation (2.1\u00b10.7 vs 2.0\u00b10.5 %MVC, respectively). Fractional glucose uptake in BAT increased post-acclimation (from 0.035\u00b10.014 to 0.048\u00b10.012 min(-1)) while net glucose uptake trended towards an increase as well (from 163\u00b160 to 209\u00b150 nmol\u00b7g(-1)\u00b7min(-1)). Conclusions: These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT, but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb??", "given" : "S??bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu??rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "??ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr?? C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran??ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "438-446", "title" : "Increased brown adipose tissue oxidative capacity in cold-acclimated humans", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.2337/db14-1651", "ISSN" : "1939327X", "PMID" : "25677914", "abstract" : "Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT \"whitening.\"", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2388-2397", "title" : "Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^{31,75\u201379}", "plainTextFormattedCitation" : "31,75\u201379", "previouslyFormattedCitation" : "^{31,75\u201379}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,75–79. Additionally, this cold exposure protocol was found to minimize overt shivering, reduce skin temperature by at least 2.5°C and increase energy expenditure by approximately 1.8-fold ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ncomms14146", "ISSN" : "2041-1723", "PMID" : "28134339", "abstract" : "In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 \u00b0C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid ((18)FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Communications", "id" : "ITEM-2", "issue" : "14146", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "title" : "Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1113/jphysiol.2014.283598", "ISBN" : "0022-3751", "ISSN" : "1469-7793", "PMID" : "25384777", "abstract" : "KEY POINTS: Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering. Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men. Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized. ABSTRACT: Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold-defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U-(13) C]-palmitate and [3-(3) H]-glucose tracer methodologies coupled with positron emission tomography using (11) C-acetate and (18) F-fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold-induced increase in whole-body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 \u00b1 124 vs. 12 \u00b1 8 \u03bcmol min(-1) , respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WA\u2026", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "701-14", "title" : "Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men.", "type" : "article-journal", "volume" : "593" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2013-3901", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "19457197", "PMID" : "24423363", "abstract" : "Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild-cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes (T2D), which may have important pathological and therapeutic implications. Although, many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Objective: To determine whether four weeks of daily cold exposure could increase both the volume of metabolically active brown adipose tissue (BAT) and its oxidative capacity. Design: Six non-acclimated men were exposed to 10\u00b0C, two hours daily for four weeks (5 days/week), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with (11)C-acetate and (18)F-fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake and volume prior to and following four weeks of cold acclimation were examined under controlled acute cold exposure conditions. Results: The four-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66\u00b130 to 95\u00b128 mL, P<0.05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725\u00b10.300 to 1.591\u00b10.326 mL\u00b7sec(-1), P<0.05). Shivering intensity was not significantly different pre- compared to post-acclimation (2.1\u00b10.7 vs 2.0\u00b10.5 %MVC, respectively). Fractional glucose uptake in BAT increased post-acclimation (from 0.035\u00b10.014 to 0.048\u00b10.012 min(-1)) while net glucose uptake trended towards an increase as well (from 163\u00b160 to 209\u00b150 nmol\u00b7g(-1)\u00b7min(-1)). Conclusions: These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT, but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb??", "given" : "S??bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu??rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "??ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr?? C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran??ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "438-446", "title" : "Increased brown adipose tissue oxidative capacity in cold-acclimated humans", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.2337/db14-1651", "ISSN" : "1939327X", "PMID" : "25677914", "abstract" : "Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT \"whitening.\"", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2388-2397", "title" : "Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^{31,75\u201379}", "plainTextFormattedCitation" : "31,75\u201379", "previouslyFormattedCitation" : "^{31,75\u201379}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,75–79. Indeed, the amount of cold exposure delivered to all participants was found to be consistent irrespective of body size or sex, as reported in Appendix Section 7.2.4; pp 133. With the cold exposure protocol defined, an MRI protocol capable of detecting BAT had to be developed. In developing an MRI protocol, factors such as data acquisition, data analysis and reliability analysis need to be considered. As such, this section was divided into three parts: 1) designing an acquisition protocol specific to BAT using MRI; 2) developing an analysis or segmentation protocol that can measure BAT MRI characteristics and activity; and 3) assessing the reliability of the MRI analysis protocol. METHODS Development of BAT MRI Acquisition Protocol To develop an MRI acquisition protocol specific to BAT, a suitable MRI pulse sequence had to be defined prior to data collection. In this study, two commercially available sequences, IDEAL-IQ and LAVA-FLEX, based on fat-water imaging, were used to acquire BAT images. IDEAL-IQ is a confounder-corrected MRI sequence that provides an accurate measure of tissue triglyceride content by using multiple spectral modelling of adipose tissues while accounting for T2* decay ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.23741", "ISBN" : "6314442508", "ISSN" : "10531807", "PMID" : "25792328", "abstract" : "On February 19\u201322, the 2012 ISMRM Workshop on Fat\u2013Water Separation was held in Long Beach, California. Over 130 attendees from 13 countries convened to discuss historical aspects of water\u2013fat imaging, as well as technical and clinical developments, and remaining challenges. Among these attendees were new and established investigators. A comprehensive overview of the meeting and presentations from the 25 invited speakers at the workshop was recently published in Magnetic Resonance in Medicine (1). As illustrated in Figure 1 below, scientific interest in fat quantification using MR spectroscopy (MRS) and MR imaging (MRI) has grown steadily in the past decade. Accordingly, many of the invited lectures and scientific abstracts at the meeting focused on emerging MRS-and MRI-based methods to quantify tissue fat concentration. Applications included quantification of tissue fat concentration in organs and tissues such as liver, pancreas, skeletal muscle, heart, thymus, bone marrow, and white and brown adipose tissue, as well as the use of MRI techniques to quantify and characterize fat content for the food industry. During these lectures and ensuing discussions, a theme that emerged multiple times was the need to standardize MR-based biomarkers for assessing tissue fat concentration. While many different MR-based biomarkers may be considered for fat quantification, an informal consensus was reached at the meeting that proton-density fat-fraction (PDFF) is currently the most practical and meaningful MR-based biomarker for this purpose. Thus, the goal of this editorial is to provide a formal statement from three of the organizers of the ISMRM workshop on the choice of PDFF as the standardized MR-based biomarker for tissue fat concentration.", "author" : [ { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sirlin", "given" : "Claude B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "11" ] ] }, "page" : "1011-1014", "publisher" : "Wiley Subscription Services, Inc., A Wiley Company", "title" : "Proton density fat-fraction: A standardized mr-based biomarker of tissue fat concentration", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Asano", "given" : "Kenji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bayram", "given" : "Ersin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Huanzhou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "A GE Healthcare MR publication", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "75-78", "title" : "Quantitative Fat Imaging for Evaluating Diffuse Liver Diseases", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^36,80", "plainTextFormattedCitation" : "36,80", "previouslyFormattedCitation" : "^36,80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }36,80. In contrast, while the LAVA-FLEX sequence provides a better-quality image, its protocol does not account for any of the correction that IDEAL-IQ performs often resulting in an underestimation of fat content. Additionally, a T2* map is not generated with the use of the LAVA-FLEX sequence. Given that FF% and T2* were planned as the primary outcomes in this study, BAT MR outcomes were measured using the more accurate and advanced IDEAL-IQ sequence – though it was recognized that the clarity of the images might be somewhat inferior. All MRI scans were performed using a 3-Tesla (T) whole-body MRI scanner (Discovery 750; GE Healthcare, Waukesha, WI, USA) in the Imaging Research Centre at St. Joseph’s Healthcare Hamilton. BAT MRI scans were performed in the axial plane using a Head/Neck/Chest (HNS) coil. The axial plane was selected based on previous protocol trials that found lower incidence of fat-water swaps in images acquired axially than images acquired in the coronal plane. To ensure that the entire neck and SCV region were captured, image acquisition started at the C2/C3 disc and ended at the T4/T5 disc. * Specific MRI protocol parameters can be found in Appendix Section 7.1.4; pp 113-114Development of BAT MRI Analysis and Segmentation ProtocolUsing the data acquisition protocol described above, a series of MR images with distinct contrasts was generated: water-only, fat-only, in-phase, out-of-phase, FF% and R2* maps. T2* maps were obtained by transforming the R2* images using the equation: T2* (ms) = 1000/R2* (s1). However, in order to obtain data from these raw MR images, a segmentation protocol would first need to be developed. Given that segmentation protocols are software-specific, it is important that suitable segmentation software is selected at the onset of data analysis. In this study, Analyze Pro was used to segment MR images over other software such as SliceOmatic (commercial software) and FSLView (free software) based on its ease of use, expansive capabilities and availability of technical support. An MRI segmentation protocol was developed to measure BAT characteristics and activity in the SCV region, an active BAT depot found in adult humans ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^11\u201313", "plainTextFormattedCitation" : "11\u201313", "previouslyFormattedCitation" : "^11\u201313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11–13. The SCV was segmented in the axial plane using semi-automated and manual segmentation tools. Semi-automated techniques were used to automate processes that would normally be affected by operator bias or subjectivity. Additionally, the use of semi-automated tools was expected to reduce the amount of time in the segmentation of MR images – thereby reducing analysis time and cost. The final segmentation protocol for SCV BAT consisted of five steps, as described below:1. Application of fat mask: A fat mask was applied directly to the FF map at the C7-T1 disc by applying an image-specific threshold, based on differences in MR intensities. This process was used to isolate adipose tissues and exclude background noise from the MR image. The image at the C7-T1 disc was used as the reference for all participants as previous protocol trials have shown that the image at this disc level contained the largest amount of fat in the SCV region. Given that this tool was sensitive to the difference in fat-water signal in the MR image, it was important to select an image with good fat-water contrast to ensure adipose tissues were isolated more accurately. 2. FF threshold application: A FF threshold set at 30 to 100% was applied to the FF image to ensure that only voxels within that specific range were included in the segmentation process. This a priori definition was based on published literature data in humans that suggests that SCV BAT occupies a wide range of FF%. Additionally, in previous protocol trials, as presented in Section 3.4.1, the broad threshold (30 to 100%) was more sensitive in capturing changes in the number of FF% voxels after cold exposure than the narrow threshold (50 to 80%). * For a complete list of studies that used MR FF% to characterize BAT – refer to Appendix Section 7.1.2; pp 104-1053. Manual delineation of the SCV: Region of interest (ROI) was manually drawn over the SCV region using the “free-hand draw” tool. The SCV was chosen for BAT segmentation since this area is known to contain the largest and most active BAT depot in adults ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^11\u201313", "plainTextFormattedCitation" : "11\u201313", "previouslyFormattedCitation" : "^11\u201313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11–13. The SCV was defined by the trapezius muscle posteriorly, the sternocleidomastoid muscle medially and the clavicle inferiorly ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38. To ensure consistent segmentation between participants, the vertebral column was used as the reference for the start (C5-C6 disc) and end (T1-T2 disc) of segmentation (see Figures 5-6)C5/C6T1/T2C5/C6T1/T2Sagittal view of the start (C5/C6 disc) and end (T1/T2 disc) of BAT segmentation.C5/C6C7/T1T1/T2C5/C6C7/T1T1/T2Multi-slice segmentation of the SCV region: left (start of segmentation), right (middle of segmentation) and bottom (end of segmentation).4. Erosion of ROI: The ROIs were then post-processed using a one-time 2D 1x3 erode (jack structural element) to correct for any inherent partial volume effects in the images. This specific erosion criterion was chosen to minimize the number of eroded voxels while still ensuring partial volume effects were corrected. 5. Application of T2* mask: As the FF mask applied included tissues with FF from 30 to 100% to maximize acquisition of fat tissue, this method would not allow discrimination between different types of adipose tissues present in the SCV (i.e. mix of brown and white adipocytes). Therefore, a T2* mask was applied to the FF map to help differentiate BAT from WAT by isolating voxels from 2 to 25 ms. This specific T2* range was chosen due to previous reports that identified a T2* value of ≥ 26 ms mostly consisted of muscles, fluids and white adipocytes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37. Additionally, the lower range of 2 ms was selected due to the MR sequence’s limitation in detecting very low T2* values (i.e. lower than 2 ms).* For a complete list of studies that used MR T2* signal to characterize BAT – refer to Appendix Section 7.1.2; pp 106BAT MR Outcomes MRI scans before and after cold exposure were analyzed to characterize SCV BAT MR characteristics. MR outcomes before cold exposure were defined as pre-cold SCV BAT FF% or pre-cold SCV BAT T2*. Subsequently, MR outcomes after cooling were defined as post-cold SCV BAT FF% or post-cold SCV BAT T2*. BAT activity was defined as the decrease in FF% (SCV BAT FF% reduction) or T2* (SCV BAT T2* reduction) in the SCV after cold exposure. SCV BAT Volume was obtained by multiplying the total number of segmented voxels to the voxel size (i.e. SCV BAT Volume = # segmented voxels x voxel size) Reliability Measurement of MRI Segmentation Protocol Inter-rater reliability of BAT MR outcomes was assessed in images acquired from the first 10 participants. Reliability analysis of the segmentation protocol only included steps 1 to 3, as described in Section 3.3.2, since this test was conducted in the early stages of protocol development (prior to implementation of ROI erosion and T2* mask application). Although the subsequent steps were not included in the reliability analysis, these processes were applied using semi-automated tools. Given that the reliability analysis of the segmentation protocol already included the steps expected to introduce the greatest human error, the addition of subsequent steps in the protocol is expected to be minimal. Statistical Analysis Participant DemographicsParticipant demographics were presented as n or n (%) for categorical variables and mean (SD) or median [Q1, Q3] for skewed variables. Normality was tested using Shapiro-Wilk W-test which is designed for small sample sizes (n ≤ 50). Data that did not follow a normal distribution were either log- or square root-transformed and re-tested for normality. If the data failed to conform to a normal distribution following transformation, non-parametric tests were used for analyses. Evaluating BAT FF% ThresholdUsing paired t-tests, data from the first 10 participants enrolled in the study were used to compare the sensitivity of a narrower (50 to 80%) or a broader FF threshold (30 to 100%) in capturing changes in FF% after cold exposure. Additionally, FF% histograms were visually inspected to evaluate the effects of cold exposure on voxels at different FF% in select participants with low or high BAT activity (as measured by FF% reduction).Evaluating BAT T2* Threshold Given the lack of standardized cut-offs in using MRI to differentiate BAT activity response, the five participants with the greatest and lowest FF% reduction were categorized into high and low BAT activity groups, respectively. Independent sample t-tests were conducted to assess the effectiveness of the T2* mask in differentiating BAT from WAT by comparing BAT MR outcomes segmented with and without the T2* mask. The dichotomization of participants into either high or low BAT activity groups allowed for a better assessment of the effects of T2* mask on BAT MR outcomes. Additionally, FF% histograms were visually inspected to further assess the effects of the T2* mask on voxels at different FF% in select participants according to their BMI (normal weight vs obese) or BAT activity (low vs high). Inter-Rater Reliability Reliability of the outcome measures between raters was measured using ICC (intra-class correlation coefficient) (3,1), a two-way mixed, single measure ICC with the following assumptions: 1) each subject is assessed by each rater; 2) raters are the only raters of interest; 3) reliability is calculated on a single measurement. Both ICCagreement and ICCconsistency were conducted to measure the reliability of the segmentation protocol between raters. ICCagreement is defined as the absolute agreement between raters while ICCconsistency measures the consistency between raters by considering systematic errors (i.e. Rater A Score = Rater B Score + systematic error) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jcm.2016.02.012", "ISBN" : "1556-3707", "ISSN" : "15563707", "PMID" : "27330520", "abstract" : "Objective Intraclass correlation coefficient (ICC) is a widely used reliability index in test-retest, intrarater, and interrater reliability analyses. This article introduces the basic concept of ICC in the content of reliability analysis. Discussion for Researchers There are 10 forms of ICCs. Because each form involves distinct assumptions in their calculation and will lead to different interpretations, researchers should explicitly specify the ICC form they used in their calculation. A thorough review of the research design is needed in selecting the appropriate form of ICC to evaluate reliability. The best practice of reporting ICC should include software information, ???model,??? ???type,??? and ???definition??? selections. Discussion for Readers When coming across an article that includes ICC, readers should first check whether information about the ICC form has been reported and if an appropriate ICC form was used. Based on the 95% confident interval of the ICC estimate, values less than 0.5, between 0.5 and 0.75, between 0.75 and 0.9, and greater than 0.90 are indicative of poor, moderate, good, and excellent reliability, respectively. Conclusion This article provides a practical guideline for clinical researchers to choose the correct form of ICC and suggests the best practice of reporting ICC parameters in scientific publications. This article also gives readers an appreciation for what to look for when coming across ICC while reading an article.", "author" : [ { "dropping-particle" : "", "family" : "Koo", "given" : "Terry K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mae Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Chiropractic Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "155-163", "publisher" : "Elsevier B.V.", "title" : "A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸¹", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "⁸¹" }, "properties" : { "noteIndex" : 48 }, "schema" : "" }81. The reliability of the following SCV BAT MR outcomes (pre- and post-cold) were measured: FF%, R2* and volume. Given that R2* maps were automatically generated by the IDEAL-IQ sequence, inter-rater reliability analyses were conducted for R2* instead of T2* to reduce analysis time associated image transformation. Statistical Analysis SoftwareGraphPad Prism (version 6; GraphPad Software, La Jolla, CA, USA) and SPSS Statistics (version 23; IBM, North Castle, NY, USA) were used for all statistical analysis. RESULTSDevelopment of BAT MRI Analysis and Segmentation Protocol Evaluating BAT FF% ThresholdData from the first 10 participants in the study were used to evaluate the sensitivity of the different FF% thresholds (50 to 80% vs 30 to 100%) in measuring the change in FF% after cold exposure (See Table 1). Participant demographics (first 10 participants)Variable Name (units)N (%)Mean (SD)Min, MaxAge (years)1027.07 (6.23)20.43, 39.79SexMale9 (90.0)--Female1 (10.0)--Weight (kg)1075.58 (12.64)56.27, 98.70Height (cm)10179.3 (11.27)158.8, 198.9BMI (kg/m2)1023.46 (3.13)19.80, 30.30Waist Circumference (cm)1082.57 (10.57)68.50, 106.6Body Fat (%)1022.44 (6.54)12.40, 34.00A more significant decrease in FF% after cooling was identified when the broader threshold was applied (p = 0.0066*; mean difference = -2.98) compared to the narrower threshold (p =0.0607; mean difference = -1.11). The individualized data is presented in Figure parison of the change in FF% between a narrow and broad threshold. FF% histograms were visually evaluated to determine if there were any differences in FF distributions in select participants with respect to their BAT activity (see Appendix Section 7.2.1; pp 117-118). In the current study, participants with high BAT activity (measured by change in FF% after cold exposure) consistently showed significant changes in their FF% distribution while participants with low BAT activity showed negligible changes. Additionally, these histograms showed that decreases in voxel counts typically occurred in the higher fat-fraction ranges (70 to 90%) rather than the lower fat fraction percentages (30 to 55%). These findings may explain the lack of sensitivity of the narrower FF threshold in detecting changes in FF% after cold exposure as the lower and higher FF ranges were not captured in using this specific threshold. Evaluating BAT T2* Threshold Data from high BAT (5 subjects with the greatest decline in FF% after cold) and low BAT subjects (5 subjects with the lowest decline in FF% after cold) from the entire study cohort (n = 36) were used to determine the value of utilizing a T2* mask in isolating BAT from WAT. Participant demographics for these two groups are presented in Tables 2 and 3 respectively.Participant demographics (High BAT)Variable Name (units)N (%)Mean (SD)Min, MaxAge (years)523.17 (0.88)22.48, 24.68Sex5Male4 (80.0)--Female1 (20.0)--Weight (kg)574.48 (8.66)63.60, 81.27Height (cm)5176.4 (10.53)165.0, 188.7BMI (kg/m2)523.88 (1.04)22.40, 24.90Underweight/Normal523.88 (1.04)22.40, 24.90Overweight/Obese0--Waist Circumference (cm)579.87 (3.45)75.00, 84.37Body Fat (%)516.04 (3.99)11.70, 21.30Participant demographics (Low BAT)Variable Name (units)N (%)Mean (SD)Min, MaxAge (years)532.04 (7.72)23.59, 40.24SexMale4 (80.0)--Female1 (20.0)--Weight (kg)597.75 (26.64)59.33, 130.9Height (cm)5172.6 (10.16)158.8, 184.0BMI (kg/m2)532.46 (7.40)23.50, 44.00Underweight/Normal123.50-Overweight/Obese434.70 (6.28)30.30, 44.00Waist Circumference (cm)5103.7 (13.53)83.60, 116.6Body Fat (%)433.90 (5.45)26.20, 38.40As noted in Table 4, no differences were found in the pre- and post-cold FF% nor in the pre- and post-cold T2* with the application of a T2* mask. Importantly, MR measures of BAT activity (i.e. FF% reduction or T2* reduction) were not altered with the application of the mask. There is however a significant decline in both the pre- and post-cold SCV BAT volume. Furthermore, using FF% histograms, it was noted that the decrease in voxels mostly occurred in the higher FF ranges consistent to the range WAT normally occupies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 61 }, "schema" : "" }37. These preliminary results suggest that the T2* mask was successful in improving the exclusion of WAT in the segmentation process. Comparison of BAT MR outcomes with and without T2* mask (n = 10). VariableFF% Mask (SD)FF% + T2* Mask (SD)Mean Diff.p-valuePre-Cold FF (%)71.19 (10.06)70.12 (9.68)1.070.9057Post-Cold FF (%)67.39 (14.30)66.71 (13.93)0.680.9394Pre-Cold T2* (ms)23.74 (8.75)13.59 (1.49)10.150.2597Post-Cold T2* (ms)23.27 (9.12)12.66 (2.17)10.610.2385Pre-Cold Volume (cm3)84.21 (58.77)59.18 (33.10)25.030.0057*Post-Cold Volume (cm3)79.99 (56.32)56.8 (32.23)23.190.0104*FF% Reduction (%)3.794 (4.59)3.412 (4.56)0.380.9661T2* Reduction (ms)0.47 (2.43)0.938 (1.09)-0.470.9585To further understand the effects of the T2* mask, the participants were divided into two groups based on their BAT activity (i.e. low or high FF% reduction) as described above. With the application of the T2* mask, the decline in SCV BAT volume differed between the two groups (see Tables 5-6). Participants with low BAT activity had a 9-fold decrease in BAT SCV volume compared to those with high BAT activity after application of the T2* mask. This finding supports the supposition that the T2* mask selectively removes WAT from the volume calculation. Using this assumption, the decrease in fat volume estimates the volume of WAT present in the SCV region (i.e. Total SCV Fat Volume = SCV BAT volume + SCV WAT volume) SCV WAT volume in participants with high BAT activity. IDFF% MaskFF% + T2* MaskSCV WAT Volume003 (+)44.0237.966.06011 (+)32.2228.773.45014 (+)16.3615.400.96028 (+)53.3741.5911.78035 (+)31.6628.762.90Mean35.5330.505.03SCV WAT volume in participants with low BAT activity. IDFF% MaskFF% + T2* MaskSCV WAT Volume002 (-)144.6487.5957.05008 (-)68.4559.389.07029 (-)148.31102.1446.17030 (-)177.77102.1475.63037 (-)125.3088.0437.26Mean132.8987.8645.04Reliability of BAT MR Segmentation Protocol Images from the first 10 participants in the study were used to assess the inter-rater reliability of the segmentation protocol. The characteristics of these 10 participants were described previously in Table 1. The ICC agreement and consistency for the three raters are presented below in Tables 7-9. Using the newly developed protocol, BAT MR outcomes were found to be very reliable, as demonstrated by high ICC values before and after cold exposure. These findings suggest that inter-rater reliability is high in terms of absolute agreement and consistency. * For individual inter-rater reliability ICCs – refer to Appendix Section 7.2.2; pp 129-130 Reliability of SCV BAT FF% between three raters before and after cold exposure Pre-Cold SCV BAT FF%RaterMean (SD)ICCagreement (95% CI)ICCconsistency (95% CI)R163.47 (6.25).991 (.972, .998).993 (.979, .998)R263.91 (6.48)R363.28 (6.27)Post-Cold SCV BAT FF%RaterMean (SD)ICCagreement (95% CI)ICCconsistency (95% CI)R160.64 (8.29).995 (.983, .999).997 (.990, .999)R261.20 (8.48)R360.57 (7.95)Reliability of SCV BAT R2* between three raters before and after cold exposure Pre-Cold SCV BAT R2*RaterMean (SD)ICCagreement (95% CI)ICCconsistency (95% CI)R178.11 (8.79).917 (.784, .976).913 (.771, .975)R276.88 (9.92)R377.29 (8.89)Post-Cold SCV BAT R2*RaterMean (SD)ICCagreement (95% CI)ICCconsistency (95% CI)R183.97 (15.55).970 (.917, .992).970 (.914, .992)R283.16 (16.48)R382.15 (17.71)Reliability of SCV Volume between three raters before and after cold exposure Pre-Cold SCV VolumeRaterMean (SD)ICCagreement (95% CI)ICCconsistency (95% CI)R177.85 (42.62).987 (.964, .996).987 (.963, .996)R274.79 (45.05)R376.08 (41.67)Post-Cold SCV VolumeRaterMean (SD)ICCagreement (95% CI)ICCconsistency (95% CI)R177.76 (45.12).985 (.954, .996).987 (.963, .996)R274.15 (45.78)R379.83 (49.28)DISCUSSION As previously noted, there is a lack of detailed methodology and standardization in the use of MRI in measuring BAT outcomes. Thus, the first objective of this project was to develop a standardized MR protocol for the acquisition and segmentation of BAT in adult humans and to evaluate the inter-rater reliability of the segmentation protocol in measuring BAT outcomes.Evaluating BAT FF% ThresholdThere is no consensus in the literature with regards to the FF range that is most representative of BAT in humans. Given that a defined FF threshold can be used in animal studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00360-017-1075-8", "ISBN" : "0123456789", "ISSN" : "0174-1578", "PMID" : "28324157", "abstract" : "Obligate hibernators, such as ground squirrels, display circannual patterns which persist even under constant laboratory conditions, suggesting that they are regulated by endogenous rhythms. Brown adipose tissue (BAT) is important for thermogenesis during periodic arousals from hibernation when core body temperature rises spontaneously from 5 to 37\u2009\u00b0C. In most small eutherians BAT growth requires several weeks of cold exposure. We hypothesized that in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), a hibernator, BAT growth is regulated, in part, by an endogenous rhythm and we predicted that this growth would precede the hibernation season without cold exposure. We tested this prediction using repeated water-fat magnetic resonance imaging over a year, including the hibernation season. Thoracic BAT depots increased in volume from spring through autumn even though animals were housed at ~22\u2009\u00b0C. Subsequent cold exposure (5\u2009\u00b0C) enlarged the thoracic BAT further. The fat fraction of this tissue fell significantly during the period of peak growth, indicating relative increases in non-triglyceride components, perhaps mitochondria or vasculature. We also found that the proportion of the body consisting of white adipose tissue (WAT) increased steadily from spring through autumn, and fell throughout hibernation, mirroring changes in body mass. Unlike BAT, WAT fat fractions remained constant (near 90%) throughout the year. Future studies will evaluate the significance of photoperiod and cold exposure on the growth of these tissues. We also found tissue with a fat fraction characteristic of BAT in the head near the eyes, a potentially novel discovery that requires further confirmation.", "author" : [ { "dropping-particle" : "", "family" : "MacCannell", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinclair", "given" : "Kevin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friesen-Waldner", "given" : "Lannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKenzie", "given" : "Charles A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staples", "given" : "James F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Comparative Physiology B", "id" : "ITEM-1", "issue" : "5-6", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "759-767", "publisher" : "Springer Berlin Heidelberg", "title" : "Water\u2013fat MRI in a hibernator reveals seasonal growth of white and brown adipose tissue without cold exposure", "type" : "article-journal", "volume" : "187" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸²", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "⁸²" }, "properties" : { "noteIndex" : 57 }, "schema" : "" }82, the research group initially opted to use a 50-80% FF mask in the segmentation of the SCV region. This specific threshold was chosen based on available literature in lean and wild-type rodents before March 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/jmri.24138", "ISBN" : "2122633255", "ISSN" : "10531807", "PMID" : "23580443", "abstract" : "PURPOSE: To determine differences in fat-signal fraction (FF) from chemical-shift-encoded water-fat MRI of interscapular BAT in mice housed at different ambient temperatures (Ta ).\\n\\nMATERIALS AND METHODS: C57BL/6J male mice (8 weeks old) were singly housed at 16\u00b0C, 23\u00b0C, or 30\u00b0C (n\u2009=\u200916/group) for 4 weeks. Measures included food intake, body weight (both measured weekly) and body composition (at baseline, 2, and 4 weeks post-thermal exposure); chemical-shift-encoded water-fat MRI was performed on a 9.4 Tesla Bruker magnet with respiratory gating and anesthesia at 4 weeks post-thermal exposure.\\n\\nRESULTS: A significant inverse relationship between food intake and Ta was evidenced (P\u2009<\u20090.0001). Lean mass was similar among groups, while total fat mass was significantly different among groups ([mean\u2009\u00b1\u2009SE]: 30\u00b0C\u2009=\u20095.10\u2009\u00b1\u20090.19 g; 23\u00b0C\u2009=\u20094.18\u2009\u00b1\u20090.16 g; 16\u00b0C\u2009=\u20093.48\u2009\u00b1\u20090.54 g; P\u2009<\u20090.0001). Mean BAT-FF was positively related to Ta (means: 30\u00b0C\u2009=\u200979.4%; 23\u00b0C\u2009=\u200961.8%; 16\u00b0C\u2009=\u200950.9%; P\u2009<\u20090.0001).\\n\\nCONCLUSION: These cross-sectional results demonstrate that MRI measurement of FF within the interscapular BAT in mice reflects recent functional status of the tissue, with a lower Ta leading to a significantly reduced BAT-FF, indicative of the tissue's involvement in thermogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Yongbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1425-1433", "title" : "Measurement of interscapular brown adipose tissue of mice in differentially housed temperatures by chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^34,83", "plainTextFormattedCitation" : "34,83", "previouslyFormattedCitation" : "^34,83" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }34,83. Findings in these studies initially suggested that FF% in the interscapular region of rodents occupied a narrow range, supporting the initially defined a priori FF threshold of 50 to 80%. However, recent literature in children ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^37,38,73,74", "plainTextFormattedCitation" : "37,38,73,74", "previouslyFormattedCitation" : "^37,38,72,73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38,73,74 and adults ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-8", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-10", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "DOI" : "10.1097/RLI.0b013e31829363b8", "ISBN" : "0020-9996", "ISSN" : "0020-9996", "PMID" : "23695084", "abstract" : "OBJECTIVES: The objective of this study was to explore the use of magnetic resonance imaging (MRI) to identify and quantify active brown adipose tissue (BAT) in adult humans. 2-Deoxy-2-[F]fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography was used as a reference method to identify active BAT depots and to guide the MRI data analysis. MATERIALS AND METHODS: The ethics committee of the institute approved the protocol, and all participants provided written informed consent before participation. Both PET combined with computed tomography and MRI of BAT were performed in 11 healthy volunteers. Brown adipose tissue was activated by cooling the participants using a dedicated water-perfused suit. For the MRI examination of BAT, water-fat imaging and dynamic T2* imaging were performed at an effective temporal resolution of 2 minutes per volume. Water-fat images were derived from a multiecho MRI sequence using the Dixon technique. RESULTS: 2-Deoxy-2-[F]fluoro-D-glucose-PET identified active BAT in 8 of the 11 participants. Water-fat MRI showed that BAT depots had a fat fraction of 65.2% (7.0%) compared with 81.5% (5.4%) for the subcutaneous white adipose tissue (paired difference of 16.3% [4.9%]; P < 0.05). Dynamic T2* imaging during cold stimulation revealed signal fluctuations that were sensitive to BAT activation. The presence of these components correlated with BAT activation quantified from FDG-PET (r = 0.63; P < 0.05). CONCLUSIONS: Although FDG-PET has superior contrast for identifying active BAT, the MRI temporal resolution provides insight in activation dynamics. In addition, the flexibility of MRI allows for simultaneous mapping of tissue fat content and functional responses. The results indicate that MRI is a promising addition to PET for the identification of BAT and its activity responses to stimulation. An MRI-based methodology to quantify BAT activity is a highly desirable step in addressing the role of BAT in obesity disorders.", "author" : [ { "dropping-particle" : "", "family" : "Rooijen", "given" : "Bart D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lans", "given" : "Anouk A.J.J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "Boudewijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wildberger", "given" : "Joachim E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottaghy", "given" : "Felix M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Backes", "given" : "Walter H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Investigative Radiology", "id" : "ITEM-11", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "page" : "708-714", "title" : "Imaging Cold-Activated Brown Adipose Tissue Using Dynamic T2*-Weighted Magnetic Resonance Imaging and 2-Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{37,66\u201373,44,84}", "plainTextFormattedCitation" : "37,66\u201373,44,84", "previouslyFormattedCitation" : "^{37,65\u201372,74,84}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,66–73,44,84 provide strong supporting data that BAT in the SCV region occupies a broad FF range, suggesting that SCV BAT cannot be defined by a narrow FF range as with studies in rodents. Thus, a second FF threshold of 30 to 100% was developed to include all adipose tissues while excluding non-adipose tissues in the segmentation process. In this study, FF% reduction was significantly more in the 30 to 100% FF threshold when compared to the 50 to 80% threshold. To further evaluate these differences in the two thresholds, FF% histograms were visually inspected and showed that most of the decrease in the number of voxels occurred in the higher FF ranges (70 to 90%) while most of the increase in voxel counts occurred in the lower FF ranges (30 to 55%). These findings suggest that the use of the narrower FF threshold was not as sensitive as the broader FF threshold in characterizing BAT activity since changes in the lower and higher FF range were not being captured in the narrower FF range. Thus, the final protocol incorporated the use of a 30 to 100% FF range in the segmentation of BAT images. The challenge was that this protocol was limited in that all adipose tissues in the region were included in the segmentation process. Evaluating BAT T2* Threshold As previously noted in Section 3.3.2, the use of a 30 to 100% FF threshold included all types of adipose tissue in the SCV region which necessitated the application of a T2* mask to help differentiate BAT from WAT. Indeed, a quick review of the literature showed that there is less overlap in T2* values between BAT and WAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-4", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{37,38,66,69,71,74,44}", "plainTextFormattedCitation" : "37,38,66,69,71,74,44", "previouslyFormattedCitation" : "^{37,38,65,68,70,73,74}" }, "properties" : { "noteIndex" : 58 }, "schema" : "" }37,38,66,69,71,74,44, suggesting that T2* mask might be able to discriminate between different types of adipose tissues more effectively than FF%. Given the lack of standardized cut-offs in using T2* to define BAT, the research group opted to use a relatively wide T2* range of 2 to 25 ms ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37. This specific T2* threshold was chosen based on limitations of the current sequence in detecting very low T2* signals as well as previous findings by Hu et al. that showed a T2* value of ≥ 26 ms mostly consists of muscles, fluids and white adipocytes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37. In this study, the addition of T2* mask in the segmentation process resulted in a significantly lower number of voxels in the low BAT activity group but not in individuals with high BAT activity. Additionally, visual inspection of FF% histograms in the high BAT activity group showed that most of the decrease in voxel count occurred in the higher FF ranges, consistent with WAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 58 }, "schema" : "" }38. Findings in this study provide the first supporting data that a T2* mask (set at 2 to 25 ms) can be used to help differentiate BAT from WAT. However, it is important to note that with the limited spatial resolution of the current MR sequence, it is highly unlikely that WAT is completely excluded from the segmentation process. Inter-Rater Segmentation Reliability To date, only two papers have reported reliability measurements in the use of MRI to measure BAT outcomes, one in adults with cardiac manifestations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷²", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "⁷¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72 and the other in neonates ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0077907", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "24205024", "abstract" : "There is a major resurgence of interest in brown adipose tissue (BAT) biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fat- and water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction) were calculated. Neonatal scans (n = 22) were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same neonate. Intra- and inter-rater measures of reliability in regional BAT depot volume and fat fraction quantification were determined based on multiple segmentations by two raters. Rodent BAT was characterized as having significantly higher water content than WAT in both in situ as well as ex vivo imaging assessments. Human neonate deposits indicative of bilateral BAT in spinal, supraclavicular and axillary regions were observed. Pairwise, WAT fat fraction was significantly greater than BAT fat fraction throughout the sample (\u0394WAT-BAT = 38 %, p<10(-4)). Repeated scans demonstrated a high voxelwise correlation for fat fraction (Rall = 0.99). BAT depot volume and fat fraction measurements showed high intra-rater (ICCBAT,VOL = 0.93, ICCBAT,FF = 0.93) and inter-rater reliability (ICCBAT,VOL = 0.86, ICCBAT,FF = 0.93). This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat fraction measurements.", "author" : [ { "dropping-particle" : "", "family" : "Rasmussen", "given" : "Jerod M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Entringer", "given" : "Sonja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Annie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erp", "given" : "Theo G M", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guijarro", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oveisi", "given" : "Fariba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swanson", "given" : "James M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piomelli", "given" : "Daniele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wadhwa", "given" : "Pathik D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buss", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potkin", "given" : "Steven G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-9", "title" : "Brown adipose tissue quantification in human neonates using water-fat separated MRI", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁵", "plainTextFormattedCitation" : "85", "previouslyFormattedCitation" : "⁸⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85. It is important to note that in these studies, T2* was not used as one of the outcomes to measure BAT characteristics or activity, and therefore only reported on reliability measurements for FF%. Given that reliability measurements are specific to the study methodology employed and population enrolled, it was important for the research group to assess the reliability of the newly developed segmentation protocol. In this study, all BAT MR outcomes (i.e. pre- and post-cold images) were found to demonstrate excellent inter-rater reliability between three raters. The high inter-rater reliability reported in this project may be explained by the use of semi-automated techniques that are typically associated with less operator bias. Additionally, all raters in this study underwent data training with an experienced radiologist to ensure proper recognition of anatomical landmarks in the segmentation of images in the SCV region. Findings in this study extend the observations reported by Franssens et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷²", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "⁷¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72 where they found a moderate inter-rater reliability for the segmentation of SCV BAT FF% (ICCagreement = 0.56). The high systematic errors associated in the study conducted by Franssens et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷²", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "⁷¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72 was most likely due to the segmentation process implemented (i.e. manual segmentation) and the lack of training prior to image segmentation. In summary, it is evident from the high measured inter-rater reliability that segmentation of BAT images is minimally influenced by trained raters.ASSESSMENT OF THE NEWLY DEVELOPED PROTOCOL TO MEASURE BAT CHARACTERISTICS AND ACTIVITYBACKGROUNDIn this section, BAT MR outcomes were assessed using the newly developed MRI protocol, as described in Part 1. As previously discussed in Chapter 1, MRI can be used to detect the morphologic differences between BAT and WAT as lower values of FF and T2* are indicative of a browner phenotype ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35. As such, a crucial part of this objective was the comparison of MR characteristics of various fat pads including the SCV (largest and most active BAT depot) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^11\u201313", "plainTextFormattedCitation" : "11\u201313", "previouslyFormattedCitation" : "^11\u201313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11–13, posterior neck fat (not thought to contain BAT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 83 }, "schema" : "" }12 and abdominal subcutaneous adipose tissue (SAT; does not contain BAT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 83 }, "schema" : "" }12. Additionally, the effects of a standardized cold exposure on BAT activity, as characterized by a greater FF reduction (i.e. TG lipolysis) and T2* reduction (i.e. oxygen consumption), were used to assess the sensitivity of the MRI protocol to detect differences in BAT MR outcomes after a cold treatment. Finally, an exploratory analysis was conducted to investigate if BAT MR outcomes can be used to detect BAT activity independent of cold exposure. METHODS The primary outcome was BAT activity as described in Section 1 of this chapter. Additional measures are described below.Anthropometrics Participants wore light clothing and were asked to remove their shoes prior to their anthropometric measurements. Weight, height and waist circumference were measured three times by trained research personnel. Weight (kg) was measured using an electronic platform scale (BMI Scale Model 882; Seca, Hamburg, Deutschland). Height (cm) was measured using a wall-mounted stadiometer (Height Measuring Rod Model 240; Seca, Hamburg, Deutschland). Waist circumference (cm) was measured using a weighted measuring tape (Pull Type Spring Scale; Ohaus, Parsippany, NJ, USA) set at 750g. The tape measure was placed around their abdomen (i.e. midpoint between the costal margin and the iliac crest) and waist circumference was measured at the end of expiration. Body CompositionBody composition was assessed using a dual energy x-ray absorptiometry (DEXA) scanner (Lunar Prodigy Advance 8743; GE Healthcare, Waukesha, WI, USA), which is the gold standard for measuring body composition ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0002-9513 (Print)\\n0002-9513 (Linking)", "ISSN" : "0002-9513", "PMID" : "8997211", "abstract" : "Although dual-energy X-ray absorptiometry (DXA) is widely used in clinical research as a means of quantifying body composition, there remains at present little published information that reviews the method's underlying physical basis. Because a clear understanding of DXA physical concepts is integral to appropriate use and interpretation, we present here a three-section review that includes both relevant in vitro and in vivo experimental demonstrations. In the first section we describe the main physical principles on which DXA is based. The section that follows presents a step-by-step analysis of the DXA two-component soft tissue model. In the final section we demonstrate how knowledge of physical concepts can lead to resolution of important methodological concerns, such as the influence of hydration changes on DXA fat estimates. A thorough understanding of DXA physical concepts provides a basis for appropriate interpretation of measurement results and stimulates many new and important research questions.", "author" : [ { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Formica", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heymsfield", "given" : "S B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "941-951", "title" : "Dual-energy X-ray absorptiometry body composition model: review of physical concepts", "type" : "article-journal", "volume" : "271" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁶", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "⁸⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86. DEXA uses small doses of radiation in the form of x-rays to measure body composition. The concept is based on the unique attenuation parameters that exist in various tissues (i.e. fat, lean or soft tissue and bone minerals) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0002-9513 (Print)\\n0002-9513 (Linking)", "ISSN" : "0002-9513", "PMID" : "8997211", "abstract" : "Although dual-energy X-ray absorptiometry (DXA) is widely used in clinical research as a means of quantifying body composition, there remains at present little published information that reviews the method's underlying physical basis. Because a clear understanding of DXA physical concepts is integral to appropriate use and interpretation, we present here a three-section review that includes both relevant in vitro and in vivo experimental demonstrations. In the first section we describe the main physical principles on which DXA is based. The section that follows presents a step-by-step analysis of the DXA two-component soft tissue model. In the final section we demonstrate how knowledge of physical concepts can lead to resolution of important methodological concerns, such as the influence of hydration changes on DXA fat estimates. A thorough understanding of DXA physical concepts provides a basis for appropriate interpretation of measurement results and stimulates many new and important research questions.", "author" : [ { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Formica", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heymsfield", "given" : "S B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "941-951", "title" : "Dual-energy X-ray absorptiometry body composition model: review of physical concepts", "type" : "article-journal", "volume" : "271" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁶", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "⁸⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86. Participants were asked to wear light clothing without any metal or hard plastic prior to the scan. A hospital gown was provided to participants who had metal or hard plastic in their clothing. The procedure consisted of the participants lying supine with their arms at their sides while the researcher ensured that they were within the confines of the scanner. If the participants’ arms were not in the confines of the scan, due to body size, the participants were asked to cross their arms on top of their chest to ensure accurate measurement of their body composition. The following measures of interest were automatically generated by the DEXA scanner software: Body Fat (%), Fat Mass (kg), Lean Mass (kg). All scans were reviewed by one individual to ensure consistency.Outdoor TemperatureMean outdoor temperature at different timepoints (1 hour, 24 hours and 7 days) prior to visit 2 were obtained from data sourced from the Government of Canada at Hamilton RBG CS region (Climate ID: 6153301). This specific weather station collects weather data every 30 minutes. Cold Exposure Protocol The cold exposure protocol used in this study was adapted from project collaborators at University of Ottawa and Université de Sherbrooke where they found this specific cooling protocol was adequate to stimulate BAT activity (as measured by PET-CT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ncomms14146", "ISSN" : "2041-1723", "PMID" : "28134339", "abstract" : "In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 \u00b0C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid ((18)FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Communications", "id" : "ITEM-2", "issue" : "14146", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "title" : "Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1113/jphysiol.2014.283598", "ISBN" : "0022-3751", "ISSN" : "1469-7793", "PMID" : "25384777", "abstract" : "KEY POINTS: Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering. Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men. Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized. ABSTRACT: Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold-defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U-(13) C]-palmitate and [3-(3) H]-glucose tracer methodologies coupled with positron emission tomography using (11) C-acetate and (18) F-fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold-induced increase in whole-body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 \u00b1 124 vs. 12 \u00b1 8 \u03bcmol min(-1) , respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WA\u2026", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "701-14", "title" : "Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men.", "type" : "article-journal", "volume" : "593" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2013-3901", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "19457197", "PMID" : "24423363", "abstract" : "Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild-cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes (T2D), which may have important pathological and therapeutic implications. Although, many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Objective: To determine whether four weeks of daily cold exposure could increase both the volume of metabolically active brown adipose tissue (BAT) and its oxidative capacity. Design: Six non-acclimated men were exposed to 10\u00b0C, two hours daily for four weeks (5 days/week), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with (11)C-acetate and (18)F-fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake and volume prior to and following four weeks of cold acclimation were examined under controlled acute cold exposure conditions. Results: The four-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66\u00b130 to 95\u00b128 mL, P<0.05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725\u00b10.300 to 1.591\u00b10.326 mL\u00b7sec(-1), P<0.05). Shivering intensity was not significantly different pre- compared to post-acclimation (2.1\u00b10.7 vs 2.0\u00b10.5 %MVC, respectively). Fractional glucose uptake in BAT increased post-acclimation (from 0.035\u00b10.014 to 0.048\u00b10.012 min(-1)) while net glucose uptake trended towards an increase as well (from 163\u00b160 to 209\u00b150 nmol\u00b7g(-1)\u00b7min(-1)). Conclusions: These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT, but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb??", "given" : "S??bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu??rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "??ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr?? C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran??ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "438-446", "title" : "Increased brown adipose tissue oxidative capacity in cold-acclimated humans", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.2337/db14-1651", "ISSN" : "1939327X", "PMID" : "25677914", "abstract" : "Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT \"whitening.\"", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2388-2397", "title" : "Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^{31,75\u201379}", "plainTextFormattedCitation" : "31,75\u201379", "previouslyFormattedCitation" : "^{31,75\u201379}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,75–79. Participants were fitted with a high-density liquid conditioned suit (LCS; Two Piece, Allen-Vanguard, Ottawa, ON, Canada) where 18°C water was circulated for 3 hours using a temperature- and flow-controlled circulation bath (Isotemp 6200 R28, Fisher Scientific, Waltham, MA, USA). The same suit was used for all participants to ensure consistent tubing density. Abdominal Subcutaneous Adipose Tissue Abdominal MRI scans were acquired in the axial plane using a 32-channel torso array coil (NeoCoil, Pewaukee, WI, USA). These scans were conducted in a breath-hold (approximately 18 seconds) as previous protocol trials have showed that breathing introduces considerable motion artefacts. Image acquisition was set to acquire 7 cm below and above the L4-L5 disc to ensure that most of the abdomen was included in the MR image. For calculation of abdominal SAT, a single-slice segmentation that separated subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and retroperitoneal adipose tissue (RPAT) was performed on the image centered at the L4-L5 disc. This has been previously shown to accurately estimate total SAT volume (see Figure 8) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "00029165", "PMID" : "17284730", "abstract" : "A single axial image measured between the 4th and 5th lumbar vertebrae (L4-L5) is most frequently chosen to approximate total abdominal visceral adipose tissue (VAT) volume, but growing evidence suggests that this measurement site is not ideal.", "author" : [ { "dropping-particle" : "", "family" : "Demerath", "given" : "Ellen W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Miryoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choh", "given" : "Audrey C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czerwinski", "given" : "Stefan A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siervogel", "given" : "Roger M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towne", "given" : "Bradford", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Clinical Nutrition", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "362-368", "title" : "Approximation of total visceral adipose tissue with a single magnetic resonance image", "type" : "article-journal", "volume" : "85" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/jid.2014.371", "ISBN" : "1046-7890", "ISSN" : "10467890", "PMID" : "24597427", "abstract" : "In a previous article,1 l attempted to assess the likely Impact of the most prominent versions of the therapeutic misconception (TM) on research subjects' informed consent. I concluded that the TM is not nearly as significant a concern as is commonly thought, and that focusing on it is more likely to undermine than promote research subjects' informed consent. A recent commentary rejects these conclusions, as least as they pertain to the \"consensus\" definition of the TM.2 The authors of the commentary argue that work on the TM remains central to ensuring the appropriateness of research subjects' consent and, by implication, the ethical acceptability of clinical research. The present work evaluates the arguments offered in support of these claims. This analysis reveals that the authors offer few substantive responses to my arguments, and the responses they do offer fail to undermine my prior conclusions. Furthermore, consideration of an additional issue-the emergence of learning healthcare systems-suggests that the TM is likely to be even less significant in the future, hence, focusing on it may be even more problematic than I argued previously. \u00a92013 by The Journal of Clinical Ethics. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Wendler", "given" : "David S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Ethics", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "387-394", "title" : "Problems with the consensus definition of the therapeutic misconception", "type" : "article-journal", "volume" : "24" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^87,88", "plainTextFormattedCitation" : "87,88", "previouslyFormattedCitation" : "^87,88" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }87,88. Additionally, given the considerably larger surface area in the abdomen, the ROI was eroded using a 2D 3x3 jack structural element to attenuate partial volume effects. * Detailed analysis and segmentation protocol for abdominal SAT are outlined in Appendix Section 7.1.5; pp 115Single-slice segmentation at the L4-L5 disc where SAT (red), VAT (green) and RPAT (yellow).Abdominal SAT MR Outcomes Abdominal SAT MR outcomes prior to cold exposure were analyzed and were defined as abdominal SAT FF% and abdominal SAT T2*.Posterior Neck SATThe segmentation process of the posterior neck SAT was similar to that of BAT segmentation, as described in Part 1, with exception of the location and the exclusion of the T2* mask application. Posterior neck SAT was defined posteriorly to the trapezius and anteriorly along the following vertebral discs: C5-C6, C6-C7 and C7-T1. This fat pad was not known to contain any BAT and was included in the same MR image acquired for BAT imaging ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }12. * Detailed analysis and segmentation protocol for posterior neck fat are outlined in Appendix Section 7.1.5; pp 116Posterior Neck SAT MR OutcomesMRI scans before and after cold exposure were analyzed to characterize posterior neck SAT MR outcomes. MR outcomes before cold exposure were defined as pre-cold posterior neck SAT FF% and pre-cold posterior neck SAT T2*. Subsequently, MR outcomes after cooling were defined as post-cold posterior neck SAT FF% and post-cold posterior neck SAT T2*. Posterior neck SAT FF% reduction and posterior neck SAT T2* reduction were defined as the decrease in FF% or T2* after cold exposure, respectively. Statistical Analysis Participant Demographics Participant demographics were presented as n or n (%) for categorical variables and mean (SD) or median [Q1, Q3] for skewed variables. Normality was tested using Shapiro-Wilk W-test which is designed for small sample sizes (n ≤ 50). Data that did not follow a normal distribution were either log- or square root-transformed and re-tested for normality. If the data failed to conform to a normal distribution following transformation, non-parametric tests were used for analyses. Comparison of MR Characteristics in Various Fat Pads To investigate how MR characteristics compare in various fat pads, FF% values were compared in the SCV, posterior neck fat and abdominal SAT. These comparisons were made using Mann-Whitney U test given that posterior neck fat and abdominal SAT were found to be non-normally distributed. Additionally, FF% histograms were generated to visually assess if FF% distributions between the three fat pads were different in select participants according to their BMI (normal weight vs obese). Effects of Cold Exposure on MR Outcomes in the SCV or Posterior Neck Paired t-tests were used to determine the effectiveness of the cold exposure protocol in stimulating BAT activity as measured by the change in FF% and T2* after cooling. Given that posterior neck SAT was non-normally distributed, a Wilcoxon Signed-Rank test was used to determine the effects of cooling on FF% and T2* in this region. Ability to Predict BAT Activity without Cold Exposure Pearson correlation test was used to determine if there was any association between pre-cold and post-cold MR outcomes to examine if pre-cold FF% or pre-cold T2* could predict BAT activity independent of cold exposure. RESULTS Participant DemographicsIn total, 36 participants completed the two required visits with all measures completed (see Table 10). The median age was 24.78 [8.78] years old and 63.9% were males. The median BMI was 23.60 [21.60, 29.10] and 36.1% participants were classified as overweight or obese. It is important to note that body composition data was not collected for one participant due to limitations of the DEXA scanner (i.e. above the weight threshold). Participant Demographics (entire study cohort; n=36)Variable Name (units)N (%)Mean (SD) or Median [Q1, Q3]Min, MaxAge (years)3624.78 [22.73, 31.02]18.96, 57.5018-2925 (69.44)23.59 [21.93, 25.37]18.96, 28.0430-408 (22.22)36.20 [31.19, 40.13]30.56, 40.38≥ 413 (8.33)50.1149.56, 57.50SexMale23 (63.9)--Female13 (36.1)--Weight (kg)3672.27 [61.10, 87.13]50.80, 130.87Height (cm)36173.38 (9.17)158.07, 198.93BMI (kg/m2)3623.60 [21.60, 29.10]18.2, 44.0Underweight/Normal 2322.10 [20.90, 23.50]18.2, 24.9Overweight/Obese1330.40 [27.95, 33.55]25.4, 44.0Waist Circumference(cm)3680.72 [73.17, 95.13]62.17, 121.73Body Fat (%)3526.59 (10.41)11.7, 47.7Fat Mass (kg)3516.53 [11.19, 31.49]7.12, 45.65Lean Mass (kg)3551.92 (9.25)33.33, 67.86Comparison of MR Characteristics in Various Fat PadsFF% values in the SCV region were compared to posterior neck SAT and abdominal SAT. As the largest BAT depot in adults, SCV was expected to have a lower FF% when compared to subcutaneous fat depots. This was, however, only observed in abdominal SAT (see Tables 11-12). These findings suggest that posterior neck SAT may contain BAT, although it is either inactive or only weakly parison of MR characteristics between SCV BAT and posterior neck SAT.VariableMedian [Q1, Q3]Median Differencep-valueSCV BATPosterior Neck SATPre-Cold FF%69.80 [65.31, 77.69]76.02 [60.33, 85.46]6.220.3535Comparison of MR characteristics between SCV BAT and abdominal SAT.VariableMedian [Q1, Q3]Median Differencep-valueSCV BATAbdominal SATPre-Cold FF%69.80 [65.31, 77.69]89.31 [84.01, 91.50]19.51<0.0001*FF% histograms were generated to assess if differences in FF% distributions existed between the three different fat pads in select participants (see Appendix Section 7.2.1; pp 119-124). Irrespective of BMI, the FF% distributions between SCV BAT and abdominal SAT were found to be visually different. In contrast, differences in FF% distributions between SCV BAT and posterior neck SAT were only apparent in participants who were obese. Effects of Cold Exposure on MR Outcomes in the SCV or Posterior Neck FF% and T2* decreased significantly after cold exposure (mean difference = -2.97; p < 0.0001*) and (mean difference = -0.84; p < 0.0001*) respectively (see Figure 9). These results suggest that the current cooling protocol was sufficient to elicit changes in BAT activity as measured by MRI. Comparison of SCV BAT FF% and SCV BAT T2* before and after cold exposure. There was no decline in the FF% of posterior neck SAT, which has not been shown to contain BAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }12, after cold exposure (median difference = -0.50; p = 0.4167). In contrast, posterior neck T2* values significantly increased after cold exposure (median difference = 0.79; p = 0.0096*) (see Figure 10). The implication of these findings is examined in the discussion section. Comparison of Posterior Neck SAT FF% and Posterior Neck SAT T2* before and after cold exposure. Ability to Predict BAT Activity without Cold Exposure A negative correlation was found between pre-cold FF% and FF% reduction (r = -0.68, p < 0.0001*) (see Figure 11). Thus, the greatest FF% reduction was seen in those with the lowest pre-cold FF%.Correlation between pre-cold FF% and FF% reduction. In contrast, no relationship was found between pre-cold T2* and T2* reduction (r = -0.06; p = 0.7410) (see Figure 12). The potential significance of these findings is discussed below.Correlation between pre-cold T2* and T2* reduction. DISCUSSION Comparison of MR Characteristics in Various Fat PadsAs previously described in Chapter 1, MRI can be used to detect the intrinsic morphological differences between BAT and WAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35. As such, it was important to assess if the newly developed segmentation protocol could detect differences in MR characteristics between different fat pads known to contain BAT or WAT. In this study MR characteristics were compared between the SCV (largest and most active BAT depot) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00691.2006.", "ISBN" : "0193-1849", "ISSN" : "0193-1849; 0193-1849", "PMID" : "17473055", "abstract" : "The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.", "author" : [ { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson", "given" : "Tore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology Endocrinology Metabolism", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "444-452", "title" : "Unexpected evidence for active brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "293" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^11\u201313", "plainTextFormattedCitation" : "11\u201313", "previouslyFormattedCitation" : "^11\u201313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11–13, posterior neck fat (not known to contain active BAT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 83 }, "schema" : "" }12 and abdominal SAT (does not contain BAT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 83 }, "schema" : "" }12. As BAT is expected to have lower FF% than WAT, it was surprising that pre-cold FF% values were not significantly different between the SCV BAT and posterior neck fat. Perhaps the posterior neck fat pad does contain some BAT, further investigation of this region is warranted to explain the findings reported in this study. It is very likely that BAT located in the posterior neck fat is either inactive or only weakly activated as 18F-FDG PET-CT studies have not shown the presence of active BAT in this area ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1430", "ISBN" : "1939-327X (Electronic)\\r0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "23704519", "abstract" : "We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symonds", "given" : "Michael E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1783-1790", "title" : "Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 83 }, "schema" : "" }12. The presence of BAT in the posterior neck fat may be explained by the interscapular BAT depot that exists during infancy but is thought to regress with age ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MOL.0b013e3283425243", "ISBN" : "1476-5497 (Electronic)\\r0307-0565 (Linking)", "ISSN" : "0957-9672", "PMID" : "21157334", "abstract" : "Human brown adipose tissue (BAT) has recently found to be functionally active in adults. The purpose of this review is to chart the importance of BAT in the light of recent publications in humans.", "author" : [ { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Lipidology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "2" ] ] }, "page" : "49-54", "title" : "Brown adipose tissue in humans", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹", "plainTextFormattedCitation" : "9", "previouslyFormattedCitation" : "⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }9. Based on these findings, a speculation can be made that in adult humans, the regression of the interscapular BAT depot with age may be related more to a decline in glucose uptake and/or metabolic activity than the disappearance of the tissue itself. This was confirmed in the current study where FF% in the posterior neck SAT did not change after cold exposure, suggesting a lack of BAT activity in this fat depot. In contrast, FF% values in the abdominal SAT were significantly higher than values found in the SCV region. Indeed, FF% histograms showed contrastingly different distributions between SCV BAT and abdominal SAT where the latter had a distribution skewed to higher FF%, consistent with WAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35. Taken together, these findings suggest strongly that abdominal SAT is void of any BAT, consistent with previous 18F-FDG PET-CT studies that did not show any active BAT in this area. These new findings, however, pose complications in the current state of the literature as most MR studies have used regions located near the previous BAT-rich interscapular depot as a comparison to the SCV region ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-7", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-10", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{37,38,66\u201370,72,74,44}", "plainTextFormattedCitation" : "37,38,66\u201370,72,74,44", "previouslyFormattedCitation" : "^{37,38,65\u201369,71,73,74}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38,66–70,72,74,44. Additionally, detailed analysis and segmentation protocol for WAT is lacking in the field ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-8", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-9", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-10", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-11", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-12", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{37,38,66\u201374,44}", "plainTextFormattedCitation" : "37,38,66\u201374,44", "previouslyFormattedCitation" : "^{37,38,65\u201374}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38,66–74,44 and not all fat depots exhibit the same FF% and/or T2* signatures as shown in this study. Indeed, in reviewing other published studies, it was noted that gluteal and abdominal fat ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^71,73", "plainTextFormattedCitation" : "71,73", "previouslyFormattedCitation" : "^70,72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71,73 were most consistent with FF% values reportedly associated with WAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35, whereas FF% in fat depots posterior to the trapezius or adjacent to the SCV were more similar to MR signatures present in the SCV BAT region ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35. Based on these findings, researchers are cautioned in using only the fat pads close to the interscapular depot as a comparison to SCV BAT as they have more similar non-cold stimulated MR signatures than abdominal SAT. Effects of Cold Exposure on MR Outcomes in the SCV or Posterior Neck As previously noted in Part 1, the cold exposure protocol used in this study was adapted from project collaborators that have previously shown that this protocol was sufficient to stimulate BAT activity (as measured by 18F-FDG uptake) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ncomms14146", "ISSN" : "2041-1723", "PMID" : "28134339", "abstract" : "In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 \u00b0C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid ((18)FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Communications", "id" : "ITEM-2", "issue" : "14146", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "title" : "Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1113/jphysiol.2014.283598", "ISBN" : "0022-3751", "ISSN" : "1469-7793", "PMID" : "25384777", "abstract" : "KEY POINTS: Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering. Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men. Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized. ABSTRACT: Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold-defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U-(13) C]-palmitate and [3-(3) H]-glucose tracer methodologies coupled with positron emission tomography using (11) C-acetate and (18) F-fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold-induced increase in whole-body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 \u00b1 124 vs. 12 \u00b1 8 \u03bcmol min(-1) , respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WA\u2026", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "701-14", "title" : "Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men.", "type" : "article-journal", "volume" : "593" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2013-3901", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "19457197", "PMID" : "24423363", "abstract" : "Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild-cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes (T2D), which may have important pathological and therapeutic implications. Although, many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Objective: To determine whether four weeks of daily cold exposure could increase both the volume of metabolically active brown adipose tissue (BAT) and its oxidative capacity. Design: Six non-acclimated men were exposed to 10\u00b0C, two hours daily for four weeks (5 days/week), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with (11)C-acetate and (18)F-fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake and volume prior to and following four weeks of cold acclimation were examined under controlled acute cold exposure conditions. Results: The four-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66\u00b130 to 95\u00b128 mL, P<0.05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725\u00b10.300 to 1.591\u00b10.326 mL\u00b7sec(-1), P<0.05). Shivering intensity was not significantly different pre- compared to post-acclimation (2.1\u00b10.7 vs 2.0\u00b10.5 %MVC, respectively). Fractional glucose uptake in BAT increased post-acclimation (from 0.035\u00b10.014 to 0.048\u00b10.012 min(-1)) while net glucose uptake trended towards an increase as well (from 163\u00b160 to 209\u00b150 nmol\u00b7g(-1)\u00b7min(-1)). Conclusions: These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT, but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb??", "given" : "S??bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu??rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "??ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr?? C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran??ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "438-446", "title" : "Increased brown adipose tissue oxidative capacity in cold-acclimated humans", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.2337/db14-1651", "ISSN" : "1939327X", "PMID" : "25677914", "abstract" : "Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT \"whitening.\"", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2388-2397", "title" : "Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^{31,75\u201379}", "plainTextFormattedCitation" : "31,75\u201379", "previouslyFormattedCitation" : "^{31,75\u201379}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,75–79. However, no studies have shown the effects of this cooling protocol on measures of BAT activity with the use of MRI technology. Given that the mechanism in which MRI measures BAT activity is entirely different than 18F-FDG PET-CT, it was important for the research group to assess the effects of this specific cold exposure protocol on BAT MR outcomes. In this study, the change in FF% after cold exposure was slightly higher than most values found in the literature ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{66,67,69\u201371,44}", "plainTextFormattedCitation" : "66,67,69\u201371,44", "previouslyFormattedCitation" : "^{65,66,68\u201370,74}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66,67,69–71,44. Other MRI studies have reported a decrease in FF% ranging from 0.4 to 2.2 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^66,71,44", "plainTextFormattedCitation" : "66,71,44", "previouslyFormattedCitation" : "^65,70,74" }, "properties" : { "noteIndex" : 75 }, "schema" : "" }66,71,44. This may be attributable to the difference in the cooling protocol (i.e. duration, temperature and method of cold delivery) used to stimulate BAT activity. In contrast to other studies, the cooling protocol used in this study was not only longer in duration and lower in temperature, but also made use of a direct-to-skin water-cooling system that covered the entire body. Given that other studies use either air-cooling or cooling blankets that only span the abdomen ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpregu.00021.2014", "ISBN" : "1522-1490 (Electronic)\\r0363-6119 (Linking)", "ISSN" : "0363-6119", "PMID" : "24871967", "abstract" : "The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the \u201cfixed volume\u201d methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "A. A. J. J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierts", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "W. D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Regulatory, Integrative and Comparative Physiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "103-113", "title" : "Cold-activated brown adipose tissue in human adults: methodological issues", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "²⁵" }, "properties" : { "noteIndex" : 73 }, "schema" : "" }25, the higher FF% change after cold exposure may be attributable to the increased surface area covered by the cold delivery system used in this study. Additionally, the newly developed segmentation protocol may have greater sensitivity to detect BAT activity based on its ability to measure a broad range of FF% changes ranging from -1.80 to 9.86%. These findings suggest that this study protocol could be used to differentiate participants with varying BAT activity (i.e. low or high BAT activity), making it a suitable modality to detect BAT in future therapeutic studies. Surprisingly, FF% increased in the SCV region after cold exposure in some participants. Given that BAT activation is characterized by an increase in both thermogenesis-induced TG lipolysis and thermogenesis-independent perfusion, the observed increase in SCV BAT FF% after cold exposure may be attributable to increased perfusion associated with BAT activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.116.186460", "ISBN" : "4934197133", "ISSN" : "0161-5505", "PMID" : "28082439", "abstract" : "(18)F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain whether BAT (18)F-FDG uptake reliably tracks UCP1-mediated heat production. METHODS UCP1 knockout (UCP1 KO) and wild-type mice received the selective \u03b23 adrenergic receptor agonist CL 316, 243 (1mg/kg) and underwent metabolic cage, infrared thermal imaging and (18)F-FDG PET/magnetic resonance imaging (MRI) experiments. Primary brown adipocytes were additionally examined for their bioenergetics as well as their uptake of 2-deoxy-3H-glucose. RESULTS In response to CL 316, 243 treatments, oxygen consumption and BAT thermogenesis were diminished in UCP1 KO mice but BAT (18)F-FDG uptake was fully retained. UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected. CONCLUSION Increased BAT (18)F-FDG uptake can occur independently of UCP1 function.", "author" : [ { "dropping-particle" : "", "family" : "Hankir", "given" : "Mohammed K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kranz", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keipert", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiner", "given" : "Juliane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andreasen", "given" : "Sille G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patt", "given" : "Marianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kl\u00f6ting", "given" : "Nora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiker", "given" : "John T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brust", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hesse", "given" : "Swen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jastroch", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fenske", "given" : "Wiebke K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1100-1103", "title" : "Dissociation Between Brown Adipose Tissue ¹⁸ F-FDG Uptake and Thermogenesis in Uncoupling Protein 1\u2013Deficient Mice", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db14-1651", "ISSN" : "1939327X", "PMID" : "25677914", "abstract" : "Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT \"whitening.\"", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2388-2397", "title" : "Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.beem.2016.09.002", "ISSN" : "15321908", "PMID" : "27697211", "abstract" : "The demonstration of the presence of metabolically active brown adipose tissue (BAT) in adult humans using positron emission tomography (PET) over the past decade has lead to the rapid development of our knowledge regarding the role of BAT in energy metabolism in animal models and in humans. Although animal models continue to provide highly valuable information regarding the mechanisms regulating BAT development, mass and metabolic functions, these studies led to many assumptions that have been at best only partially verified in humans so far. Combined to some limitations of the current investigation approaches used in humans, this has lead to speculation on the potential role of BAT dysfunction in the development of cardiometabolic disorders and on the potential of BAT metabolic activation to treat these conditions. Here we propose a critical review of the evidence for the implication of BAT in cardiometabolic health.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best Practice and Research: Clinical Endocrinology and Metabolism", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "497-513", "title" : "The role of BAT in cardiometabolic disorders and aging", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^32,79,89", "plainTextFormattedCitation" : "32,79,89", "previouslyFormattedCitation" : "^32,79,89" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32,79,89. This has previously been seen in rodent models where UCP1 KO mice demonstrated increased 18F-FDG uptake (i.e. substrate uptake) in BAT depots in the absence of BAT-induced thermogenesis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.116.186460", "ISBN" : "4934197133", "ISSN" : "0161-5505", "PMID" : "28082439", "abstract" : "(18)F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain whether BAT (18)F-FDG uptake reliably tracks UCP1-mediated heat production. METHODS UCP1 knockout (UCP1 KO) and wild-type mice received the selective \u03b23 adrenergic receptor agonist CL 316, 243 (1mg/kg) and underwent metabolic cage, infrared thermal imaging and (18)F-FDG PET/magnetic resonance imaging (MRI) experiments. Primary brown adipocytes were additionally examined for their bioenergetics as well as their uptake of 2-deoxy-3H-glucose. RESULTS In response to CL 316, 243 treatments, oxygen consumption and BAT thermogenesis were diminished in UCP1 KO mice but BAT (18)F-FDG uptake was fully retained. UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected. CONCLUSION Increased BAT (18)F-FDG uptake can occur independently of UCP1 function.", "author" : [ { "dropping-particle" : "", "family" : "Hankir", "given" : "Mohammed K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kranz", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keipert", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiner", "given" : "Juliane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andreasen", "given" : "Sille G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patt", "given" : "Marianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kl\u00f6ting", "given" : "Nora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiker", "given" : "John T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brust", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hesse", "given" : "Swen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jastroch", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fenske", "given" : "Wiebke K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1100-1103", "title" : "Dissociation Between Brown Adipose Tissue ¹⁸ F-FDG Uptake and Thermogenesis in Uncoupling Protein 1\u2013Deficient Mice", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³²", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32. Additionally, Blondin et al. demonstrated that the inhibition of TG lipolysis in adult humans abolished BAT-induced thermogenesis but still resulted in increased perfusion and substrate uptake during cold-induced BAT activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁵", "plainTextFormattedCitation" : "75", "previouslyFormattedCitation" : "⁷⁵" }, "properties" : { "noteIndex" : 74 }, "schema" : "" }75. Of note, the majority of the participants that demonstrated an increase in SCV BAT FF% after cold exposure were classified as obese, a group known to exhibit less BAT-induced thermogenesis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/db10-0004", "ISBN" : "1939-327X (Electronic)\\n0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "20357363", "abstract" : "OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.\\n\\nRESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.\\n\\nRESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09).\\n\\nCONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.", "author" : [ { "dropping-particle" : "", "family" : "Pfannenberg", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Matthias K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripkens", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stef", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deckert", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmadl", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimold", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "Hans Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claussen", "given" : "Claus D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefan", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7", "1" ] ] }, "page" : "1789-1793", "title" : "Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/oby.2010.105", "ISBN" : "1930-7381 (Print) 1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "20448535", "abstract" : "Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20\u201328 years underwent FDG-PET after 2-h cold exposure at 19 \u00b0C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 \u00b0C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 \u00b1 97 kcal/day, being comparable with that of the BAT-negative group (1,434 \u00b1 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 \u00b1 293 (P < 0.05) and slightly by 42 \u00b1 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 \u00b0C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 \u00b0C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "6" ] ] }, "page" : "13-16", "publisher" : "Nature Publishing Group", "title" : "Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/oby.20456", "ISBN" : "1930-739X (Electronic)\\r1930-7381 (Linking)", "ISSN" : "19307381", "PMID" : "23554353", "abstract" : "OBJECTIVE: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. DESIGN AND METHODS: Using positron emission tomography (PET), we quantified cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans. Further, cold-induced glucose uptake was measured in obese subjects before and after a five-month conventional weight loss. RESULTS: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. CONCLUSIONS: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.", "author" : [ { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noponen", "given" : "Tommi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viljanen", "given" : "Tapio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-6", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2279-2287", "title" : "Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1056/NEJMoa0808718", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357405", "abstract" : "Background Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. Methods We studied 24 healthy men \u2014 10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], <25) and 14 who were overweight or obese (BMI, \u226525) \u2014 under thermoneutral conditions (22\u00b0C) and during mild cold exposure (16\u00b0C). Putative brown-adipose-tissue activity was ...", "author" : [ { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanhommerig", "given" : "Joost W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smulders", "given" : "Nanda M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossaerts", "given" : "Jamie M.A.F.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemerink", "given" : "Gerrit J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouvy", "given" : "Nicole D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teule", "given" : "G.J. Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-7", "issue" : "15", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1500-1508", "title" : "Cold-Activated Brown Adipose Tissue in Healthy Men", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.2967/jnumed.112.117275", "ISBN" : "1535-5667", "ISSN" : "1535-5667", "PMID" : "23868958", "abstract" : "UNLABELLED:The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging.\\n\\nMETHODS:BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge.\\n\\nRESULTS:Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% \u00b1 1.8% (P < 0.01).\\n\\nCONCLUSION:We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Yin-Ching Iris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yih-Chieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwong", "given" : "Kenneth K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "id" : "ITEM-9", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "1584-1587", "publisher" : "Society of Nuclear Medicine", "title" : "Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{5,6,11,17\u201322}", "plainTextFormattedCitation" : "5,6,11,17\u201322", "previouslyFormattedCitation" : "^{5,6,11,17\u201322}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,6,11,17–22. Altogether, these findings suggest that BAT-induced thermogenesis is either inactive or weakly activated in these individuals and the marked increase in FF% is due to increased perfusion and thereby substrate uptake during BAT activation.As previously stated in Chapter 1, changes in the ratio of oxy- and deoxy-haemoglobin concentration associated with BAT activation can be captured by the T2* signal ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/rg.295095034", "ISBN" : "1527-1323 (Electronic)\\r0271-5333 (Linking)", "ISSN" : "0271-5333", "PMID" : "19755604", "abstract" : "T2* relaxation refers to decay of transverse magnetization caused by a combination of spin-spin relaxation and magnetic field inhomogeneity. T2* relaxation is seen only with gradient-echo (GRE) imaging because transverse relaxation caused by magnetic field inhomogeneities is eliminated by the 180 degrees pulse at spin-echo imaging. T2* relaxation is one of the main determinants of image contrast with GRE sequences and forms the basis for many magnetic resonance (MR) applications, such as susceptibility-weighted (SW) imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be made predominantly T2* weighted by using a low flip angle, long echo time, and long repetition time. GRE sequences with T2*-based contrast are used to depict hemorrhage, calcification, and iron deposition in various tissues and lesions. SW imaging uses phase information in addition to T2*-based contrast to exploit the magnetic susceptibility differences of the blood and of iron and calcification in various tissues. Perfusion MR imaging exploits the signal intensity decrease that occurs with the passage of a high concentration of gadopentetate dimeglumine through the microvasculature. Change in oxygen saturation during specific tasks changes the local T2*, which leads to the blood oxygen level-dependent effect seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted sequences, and their clinical applications are presented, followed by the principles, techniques, and clinical uses of four T2*-based applications, including SW imaging, perfusion MR imaging, functional MR imaging, and iron overload imaging", "author" : [ { "dropping-particle" : "", "family" : "Chavhan", "given" : "Govind B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babyn", "given" : "Paul S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Bejoy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shroff", "given" : "Manohar M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haacke", "given" : "E. Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RadioGraphics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1433-1449", "publisher" : "Radiological Society of North America", "title" : "Principles, Techniques, and Applications of T2*-based MR Imaging and Its Special Applications", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁹", "plainTextFormattedCitation" : "39", "previouslyFormattedCitation" : "³⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39. There has been limited research in the use of MR T2* signal to measure cold-induced BAT activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^66,71,44", "plainTextFormattedCitation" : "66,71,44", "previouslyFormattedCitation" : "^65,70,74" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66,71,44. Findings in previous studies have generally shown a trend of decreasing T2* signal after cooling, consistent with BAT activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^66,71,44", "plainTextFormattedCitation" : "66,71,44", "previouslyFormattedCitation" : "^65,70,74" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66,71,44. In this study, T2* values in the SCV region significantly decreased after the cold exposure. This finding further supports the results described previously which showed that the cold exposure protocol used in this study was sufficient in stimulating BAT activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ncomms14146", "ISSN" : "2041-1723", "PMID" : "28134339", "abstract" : "In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 \u00b0C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid ((18)FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Communications", "id" : "ITEM-2", "issue" : "14146", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "title" : "Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1113/jphysiol.2014.283598", "ISBN" : "0022-3751", "ISSN" : "1469-7793", "PMID" : "25384777", "abstract" : "KEY POINTS: Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering. Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men. Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized. ABSTRACT: Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold-defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U-(13) C]-palmitate and [3-(3) H]-glucose tracer methodologies coupled with positron emission tomography using (11) C-acetate and (18) F-fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold-induced increase in whole-body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 \u00b1 124 vs. 12 \u00b1 8 \u03bcmol min(-1) , respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WA\u2026", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "701-14", "title" : "Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men.", "type" : "article-journal", "volume" : "593" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2013-3901", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "19457197", "PMID" : "24423363", "abstract" : "Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild-cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes (T2D), which may have important pathological and therapeutic implications. Although, many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Objective: To determine whether four weeks of daily cold exposure could increase both the volume of metabolically active brown adipose tissue (BAT) and its oxidative capacity. Design: Six non-acclimated men were exposed to 10\u00b0C, two hours daily for four weeks (5 days/week), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with (11)C-acetate and (18)F-fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake and volume prior to and following four weeks of cold acclimation were examined under controlled acute cold exposure conditions. Results: The four-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66\u00b130 to 95\u00b128 mL, P<0.05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725\u00b10.300 to 1.591\u00b10.326 mL\u00b7sec(-1), P<0.05). Shivering intensity was not significantly different pre- compared to post-acclimation (2.1\u00b10.7 vs 2.0\u00b10.5 %MVC, respectively). Fractional glucose uptake in BAT increased post-acclimation (from 0.035\u00b10.014 to 0.048\u00b10.012 min(-1)) while net glucose uptake trended towards an increase as well (from 163\u00b160 to 209\u00b150 nmol\u00b7g(-1)\u00b7min(-1)). Conclusions: These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT, but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb??", "given" : "S??bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu??rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "??ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr?? C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran??ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "438-446", "title" : "Increased brown adipose tissue oxidative capacity in cold-acclimated humans", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.2337/db14-1651", "ISSN" : "1939327X", "PMID" : "25677914", "abstract" : "Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT \"whitening.\"", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kunach", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2388-2397", "title" : "Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^{31,75\u201379}", "plainTextFormattedCitation" : "31,75\u201379", "previouslyFormattedCitation" : "^{31,75\u201379}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,75–79. However, these results conflict with the study conducted by Chen et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.112.117275", "ISBN" : "1535-5667", "ISSN" : "1535-5667", "PMID" : "23868958", "abstract" : "UNLABELLED:The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging.\\n\\nMETHODS:BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge.\\n\\nRESULTS:Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% \u00b1 1.8% (P < 0.01).\\n\\nCONCLUSION:We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Yin-Ching Iris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yih-Chieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwong", "given" : "Kenneth K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "1584-1587", "publisher" : "Society of Nuclear Medicine", "title" : "Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 84 }, "schema" : "" }22 where they found a 10.7% increase in blood-oxygen-level dependent (BOLD) signal after 1 hour of cold exposure in three participants (all females with normal BMI) with detectable BAT activity (via 18F-FDG PET-CT). BOLD is a T2*-based functional MR imaging technique capable of detecting changes in deoxyhemoglobin content where an increase in BOLD signal reflects a lower deoxyhemoglobin content (i.e. higher T2* signal) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/rg.295095034", "ISBN" : "1527-1323 (Electronic)\\r0271-5333 (Linking)", "ISSN" : "0271-5333", "PMID" : "19755604", "abstract" : "T2* relaxation refers to decay of transverse magnetization caused by a combination of spin-spin relaxation and magnetic field inhomogeneity. T2* relaxation is seen only with gradient-echo (GRE) imaging because transverse relaxation caused by magnetic field inhomogeneities is eliminated by the 180 degrees pulse at spin-echo imaging. T2* relaxation is one of the main determinants of image contrast with GRE sequences and forms the basis for many magnetic resonance (MR) applications, such as susceptibility-weighted (SW) imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be made predominantly T2* weighted by using a low flip angle, long echo time, and long repetition time. GRE sequences with T2*-based contrast are used to depict hemorrhage, calcification, and iron deposition in various tissues and lesions. SW imaging uses phase information in addition to T2*-based contrast to exploit the magnetic susceptibility differences of the blood and of iron and calcification in various tissues. Perfusion MR imaging exploits the signal intensity decrease that occurs with the passage of a high concentration of gadopentetate dimeglumine through the microvasculature. Change in oxygen saturation during specific tasks changes the local T2*, which leads to the blood oxygen level-dependent effect seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted sequences, and their clinical applications are presented, followed by the principles, techniques, and clinical uses of four T2*-based applications, including SW imaging, perfusion MR imaging, functional MR imaging, and iron overload imaging", "author" : [ { "dropping-particle" : "", "family" : "Chavhan", "given" : "Govind B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babyn", "given" : "Paul S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Bejoy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shroff", "given" : "Manohar M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haacke", "given" : "E. Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RadioGraphics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1433-1449", "publisher" : "Radiological Society of North America", "title" : "Principles, Techniques, and Applications of T2*-based MR Imaging and Its Special Applications", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁹", "plainTextFormattedCitation" : "39", "previouslyFormattedCitation" : "³⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39. Of note, there were several limitations in their study that might explain the increase in BAT T2* signal after cold exposure. First, the measure of BAT and the measure of BOLD signalling occurred 2 years apart. Considering that BAT is an extremely plastic tissue ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrendo.2016.136", "ISBN" : "1759-5037 (Electronic)\r1759-5029 (Linking)", "ISSN" : "1759-5029", "PMID" : "27616452", "abstract" : "Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and experimental studies have associated BAT activity with protection against obesity and metabolic diseases, such as type 2 diabetes mellitus and dyslipidaemia. Active BAT is present in adult humans and its activity is impaired in patients with obesity. The ability of BAT to protect against chronic metabolic disease has traditionally been attributed to its capacity to utilize glucose and lipids for thermogenesis. However, BAT might also have a secretory role, which could contribute to the systemic consequences of BAT activity. Several BAT-derived molecules that act in a paracrine or autocrine manner have been identified. Most of these factors promote hypertrophy and hyperplasia of BAT, vascularization, innervation and blood flow, processes that are all associated with BAT recruitment when thermogenic activity is enhanced. Additionally, BAT can release regulatory molecules that act on other tissues and organs. This secretory capacity of BAT is thought to be involved in the beneficial effects of BAT transplantation in rodents. Fibroblast growth factor 21, IL-6 and neuregulin 4 are among the first BAT-derived endocrine factors to be identified. In this Review, we discuss the current understanding of the regulatory molecules (the so-called brown adipokines or batokines) that are released by BAT that influence systemic metabolism and convey the beneficial metabolic effects of BAT activation. The identification of such adipokines might also direct drug discovery approaches for managing obesity and its associated chronic metabolic diseases.", "author" : [ { "dropping-particle" : "", "family" : "Villarroya", "given" : "Francesc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cereijo", "given" : "Rub\u00e9n", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Villarroya", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giralt", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Reviews Endocrinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016", "9", "12" ] ] }, "page" : "26-35", "publisher" : "Nature Research", "title" : "Brown adipose tissue as a secretory organ", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁰", "plainTextFormattedCitation" : "90", "previouslyFormattedCitation" : "⁹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }90 – there may have been changes in their BAT tissue. Additionally, the authors did not coordinate their experimental protocol with the participants’ menstrual cycle – both estrogen and progesterone have been shown to have inhibitory effects on BAT activity in rodents ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s004240050690", "ISBN" : "0031-6768 (Print)\\r0031-6768 (Linking)", "ISSN" : "00316768", "PMID" : "9716701", "abstract" : "The effects of acute and chronic acclimation to cold on uncoupling protein 1 (UCP1) levels, as well as on GDP-binding to mitochondria, cytochrome c oxidase activity and mitochondrial protein concentration in brown adipose tissue (BAT) of intact male and female rats have been analyzed. Results reveal that females rats are more sensitive to cold because their threshold temperature for the thermogenic response is set at a higher value (around 22 degreesC) than that of males (around 18 degreesC), hence leading to differences in BAT UCP1 levels between the sexes at different environmental temperatures. In vitro experiments showed that steroid hormones, beta-estradiol, estrone and progesterone, can reduce norepinephrine-induced UCP1 synthesis in brown adipocytes differentiated in primary culture. Thus the different sex-associated response of cold-induced thermogenesis in rats does not appear to be explained by a direct action of sex steroids upon the adipocyte, implying that other factors in the thermogenic regulatory system must be involved.", "author" : [ { "dropping-particle" : "", "family" : "Quevedo", "given" : "Santiago", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roca", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pic\u00f3", "given" : "Catalina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palou", "given" : "Andreu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pflugers Archiv European Journal of Physiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "689-695", "title" : "Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue", "type" : "article-journal", "volume" : "436" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹¹", "plainTextFormattedCitation" : "91", "previouslyFormattedCitation" : "⁹¹" }, "properties" : { "noteIndex" : 87 }, "schema" : "" }91. Last, the study was limited in its sample size and only included females. Thus, a combination of the above factors may explain the increase in BOLD signal in contrast to the decline in T2* signal noted in the current study. As shown in the previous section, pre-cold FF% values in the posterior neck SAT were more similar to that of SCV BAT than abdominal SAT. However, changes in FF% and T2* after cold exposure in posterior neck SAT did not follow the same trend as SCV BAT, consistent with inactive BAT. Indeed, FF% in the posterior neck did not change after cold exposure. Further, T2* values increased with cold exposure. These findings suggest that BAT-induced thermogenesis was low (i.e. no consumption of TG leading to a decline in FF%) but BAT-induced perfusion was high leading to a surplus of oxygen supply (i.e. increased T2* signal).Ability to Predict BAT Activity without Cold Exposure Preliminary findings suggest that pre-cold SCV BAT FF% can be used as a potential marker of BAT activity (as measured by FF% reduction). These results support the recent findings that showed a good correlation between pre-cold FF% and 18F-FDG uptake in 13 adults (r = -0.63) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁶", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66. Findings from this study and by Holstila et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁶", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66 provide the first supporting data on the long-held notion that MRI could be used to detect BAT activity independent of cold exposure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "¹⁶" }, "properties" : { "noteIndex" : 76 }, "schema" : "" }16. Of note, both these findings did not account for any covariates that could affect this relationship. Thus, a definite conclusion cannot be made at this time if pre-cold FF% can be directly used as a measure of BAT activity without conducting a more robust statistical analysis that accounts for potential covariates. In contrast, no relationship was found between pre-cold T2* and T2* reduction. This conflicts with results recently reported by Holstila et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁶", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66 wherein a good correlation was found between pre-cold T2* and 18F-FDG uptake (r = -0.65). The lack of relationship between pre-cold T2* and T2* reduction may be due to limitations associated with the study methodology in the current work. Due to the complexity of the experimental protocol, there was an average of a 20-minute time lag between the end of the cold exposure and the post-cold MRI scan. This time lag was due to a combination of factors that include acquiring thermographic pictures, removal of the water-perfused suit, wireless temperature loggers and EMG sensors as well as bathroom breaks. Given that BAT T2* signal is time-sensitive and has been shown to respond temporally with bouts of cold and warm exposure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/RLI.0b013e31829363b8", "ISBN" : "0020-9996", "ISSN" : "0020-9996", "PMID" : "23695084", "abstract" : "OBJECTIVES: The objective of this study was to explore the use of magnetic resonance imaging (MRI) to identify and quantify active brown adipose tissue (BAT) in adult humans. 2-Deoxy-2-[F]fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography was used as a reference method to identify active BAT depots and to guide the MRI data analysis. MATERIALS AND METHODS: The ethics committee of the institute approved the protocol, and all participants provided written informed consent before participation. Both PET combined with computed tomography and MRI of BAT were performed in 11 healthy volunteers. Brown adipose tissue was activated by cooling the participants using a dedicated water-perfused suit. For the MRI examination of BAT, water-fat imaging and dynamic T2* imaging were performed at an effective temporal resolution of 2 minutes per volume. Water-fat images were derived from a multiecho MRI sequence using the Dixon technique. RESULTS: 2-Deoxy-2-[F]fluoro-D-glucose-PET identified active BAT in 8 of the 11 participants. Water-fat MRI showed that BAT depots had a fat fraction of 65.2% (7.0%) compared with 81.5% (5.4%) for the subcutaneous white adipose tissue (paired difference of 16.3% [4.9%]; P < 0.05). Dynamic T2* imaging during cold stimulation revealed signal fluctuations that were sensitive to BAT activation. The presence of these components correlated with BAT activation quantified from FDG-PET (r = 0.63; P < 0.05). CONCLUSIONS: Although FDG-PET has superior contrast for identifying active BAT, the MRI temporal resolution provides insight in activation dynamics. In addition, the flexibility of MRI allows for simultaneous mapping of tissue fat content and functional responses. The results indicate that MRI is a promising addition to PET for the identification of BAT and its activity responses to stimulation. An MRI-based methodology to quantify BAT activity is a highly desirable step in addressing the role of BAT in obesity disorders.", "author" : [ { "dropping-particle" : "", "family" : "Rooijen", "given" : "Bart D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lans", "given" : "Anouk A.J.J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "Boudewijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wildberger", "given" : "Joachim E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottaghy", "given" : "Felix M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Backes", "given" : "Walter H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Investigative Radiology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "page" : "708-714", "title" : "Imaging Cold-Activated Brown Adipose Tissue Using Dynamic T2*-Weighted Magnetic Resonance Imaging and 2-Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁴", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "⁸⁴" }, "properties" : { "noteIndex" : 85 }, "schema" : "" }84, this time lag could potentially explain the lack of association between pre-cold T2* and T2* reduction in this study. examination of the relationship between bat characteristics and activity and known covariates (OBJECTIVE 2)BACKGROUNDThere has been limited research on the use of MRI as a modality to characterize BAT. To date, only five MR studies have used cold exposure to stimulate BAT activity; however, these studies were limited by their small sample sizes (ranging from 9 to 17) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{66,67,69\u201371,44}", "plainTextFormattedCitation" : "66,67,69\u201371,44", "previouslyFormattedCitation" : "^{65,66,68\u201370,74}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66,67,69–71,44. Additionally, the homogeneity of the populations enrolled in these studies made it impossible to assess the associations between BAT characteristics or activity and differences in participant characteristics, including known covariates of BAT ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{66,67,69\u201371,44}", "plainTextFormattedCitation" : "66,67,69\u201371,44", "previouslyFormattedCitation" : "^{65,66,68\u201370,74}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66,67,69–71,44. As such, the primary objective of this chapter was to examine the relationship between BAT MR outcomes and known covariates of BAT including age, sex, body fat percentage and outdoor temperature. As previously described in Chapter 1, BAT volume and activity (as measured by 18F-FDG PET-CT) are inversely correlated with age and body fat percentage, while the relationship between BAT outcomes with sex and outdoor temperature are inconsistent but this variance may, in part be due to inconsistent cold exposure.* For more information on known covariates of BAT – refer to Section 1.2; pp 3-5METHODSPrimary OutcomeBAT MR Outcomes As described in Part 1, MRI was used to measure BAT characteristics and activity in the SCV region. BAT characteristics were defined as MR outcomes before the cold exposure treatment (i.e. pre-cold FF% or pre-cold T2*). BAT activity was defined as the decrease in FF% (FF% reduction) or T2* (T2* reduction) in the SCV after cold exposure. * For detailed methodology on BAT outcomes – refer to Section 3.3.2; pp 30Known Covariates Factors that are known to be associated with BAT include age, sex, body fat percentage and outdoor temperature. In the current study, age and sex were self-reported and body fat percentage was measured using a DEXA scanner (for detailed methodology, refer to Section 3.7.2; pp 46). Outdoor temperature data was obtained from Environment Canada at 1 hour, 24 hours and 7 days prior to visit 2 (for detailed methodology, refer to Section 3.7.3; pp 47).Statistical Analysis Participant DemographicsParticipant demographics were presented as n or n (%) for categorical variables and mean (SD) or median [Q1, Q3] for skewed variables. All data were initially tested for normality using Shapiro-Wilk W-test designed for small sample sizes (n ≤ 50). Data that did not follow a normal distribution were either log- or square root-transformed and re-tested for normality. If the data failed to conform to a normal distribution following transformation, non-parametric tests were used for analyses. A scatter plot was used to assess the linearity of relationships. Relationship between BAT and Known Covariates Given that age was non-normally distributed, a Spearman’s rank correlation coefficient was used to examine the relationship between BAT characteristics or activity with age. The association between body fat percentage and BAT MR outcomes were assessed using Pearson correlation. An independent sample t-test was used to compare if there were differences in BAT MR outcomes between males and females. Using Pearson correlation, the relationship between outdoor temperature and BAT MR outcomes were also assessed. Multiple Regression ModelMultivariate modelling was used to examine the independent relationship of predictors or contributors to BAT characteristics or activity. The sample size was determined using the “rule of thumb” of 10 subjects per variable (SPV) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.20982/tqmp.03.2.p043", "ISBN" : "1913-4126", "ISSN" : "1913-4126", "abstract" : "This article addresses the definition of power and its relationship to Type I and Type II errors. We discuss the relationship of sample size and power. Finally, we offer statistical rules of thumb guiding the selection of sample sizes large enough for sufficient power to detecting differences, associations, chi\u2010square, and factor analyses.", "author" : [ { "dropping-particle" : "", "family" : "Wilson Van Voorhis", "given" : "Carmen R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Betsy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Tutorials in Quantitative Methods for Psychology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "43-50", "title" : "Understanding Power and Rules of Thumb for Determining Sample Sizes", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹²", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "⁹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92. As described, potential covariates of BAT include age, sex, body fat percentage and outdoor temperature. Therefore, approximately 40 participants were needed to have enough power to assess the potential relationship between each BAT MR outcome and potential covariates. Since recruitment for the study is still ongoing, an interim analysis of 36 participants was presented in this thesis. Stepwise multiple regression analysis was conducted for each BAT MR outcome (i.e. pre-cold FF%, pre-cold T2*, FF% reduction and T2* reduction), where independent variables included age and sex (model 1) and body fat percentage (model 2). This specific order was chosen to first evaluate the effects of age and sex on each BAT MR outcome, before accounting for body fat percentage. RESULTSParticipant Demographics Since the study is still ongoing, data from 36 participants was used to assess the relationship between BAT and potential covariates (see Table 13). It is important to note that due to motion artifacts present in the images, post-cold MRI data from two individuals were not included in the analysis. Body composition data was not collected for one participant due to limitations of the DEXA scanner (i.e. above the weight threshold).Participant Demographics (Objective 2)Variable Name (units)N (%)Mean (SD) or Median [Q1, Q3]Min, MaxAge (years)3624.78 [22.73, 31.02]18.96, 57.5018-2925 (69.44)23.59 [21.93, 25.37]18.96, 28.0430-408 (22.22)36.20 [31.19, 40.13]30.56, 40.38≥ 413 (8.33)50.1149.56, 57.50SexMale23 (63.9)--Female13 (36.1)--Weight (kg)3672.27 [61.10, 87.13]50.80, 130.87Height (cm)36173.38 (9.17)158.07, 198.93BMI (kg/m2)3623.60 [21.60, 29.10]18.2, 44.0Underweight/Normal 2322.10 [20.90, 23.50]18.2, 24.9Overweight/Obese1330.40 [27.95, 33.55]25.4, 44.0Waist Circumference (cm)3680.72 [73.17, 95.13]62.17, 121.73Body Fat (%)3526.59 (10.41)11.7, 47.7Fat Mass (kg)3516.53 [11.19, 31.49]7.12, 45.65Lean Mass (kg)3551.92 (9.25)33.33, 67.86Pre-Cold FF (%)3670.47 (7.93)52.75, 84.82Post-Cold FF (%)3467.78 (10.12)47.94, 86.62FF% Reduction (%)342.97 (2.71)-1.80, 9.86Pre-Cold T2* (ms)3613.66 (1.46)10.68, 16.39Post-Cold T2* (ms)3412.93 (1.74)9.44, 16.72T2* Reduction (ms)340.84 (0.90)-1.10, 3.33Outdoor Temperature 1 hour prior to visit 2 (°C)365.39 (9.98)-12.70, 29.70Outdoor Temperature 24 hours prior to visit 2 (°C)366.81 (9.43)-9.18, 27.02Outdoor Temperature 7 days prior to visit 2 (°C)366.35 (9.31)-6.59, 24.73Relationship between BAT MR Outcomes and Known Covariates No associations were found between T2* reduction and known BAT covariates and so for simplicity, study findings are presented in Appendix Section 7.2.3; pp 131-132. BAT and AgeIn examining the relationship between BAT characteristics and age, a moderate positive correlation was found between pre-cold FF% and age (r = 0.54; p = 0.0007*) as with pre-cold T2* and age (r = 0.42; p = 0.0112*) (see Figure 13). BAT MR characteristics and age Consistent with the findings in which BAT was measured with 18F-FDG PET-CT, BAT activity (as measured by FF% reduction) was negatively correlated with age (r = -0.39; p = 0.0213*) (see Figure 14). FF% reduction and ageBAT and % Body Fat Body fat percentage was strongly correlated with pre-cold FF% (r = 0.83; p < 0.0001*) and moderately correlated with pre-cold T2* (r = 0.58; p = 0.0002*) (see Figure 15). BAT MR characteristics and body fat percentage In terms of BAT activity, a moderate linear correlation existed between % body fat and FF% reduction (r = -0.64; p < 0.0001*) (see Figure 16). Thus, those with the highest body fat had the smallest decline in FF% with cold (i.e. had the lowest BAT activity).FF% reduction and body fat percentageBAT and Sex As seen in Table 14, no significant differences between males and females were found for any of the BAT MR outcomes. BAT MR outcomes and sex VariableNMean (SD)p-valueMean DifferencePre-Cold FF% Male2369.85 (7.81).542-1.71Female1371.56 (8.34)FF% Reduction Male223.32 (2.91).315.99Female122.33 (2.25)Pre-Cold T2* Male2313.59 (1.26).724-.18Female1313.77 (1.82)BAT and Outdoor Temperature As noted in Table 15, no relationship was found between outdoor temperature (different timepoints prior to visit 2) and any BAT MR outcomes. BAT MR outcomes and outdoor temperature BAT MR outcomes and outdoor temperatureOutdoor TemperatureVariableN1 hour24 hours7 daysrp-valuerp-valuerp-valuePre-Cold FF%36-0.080.6526-0.030.8447-0.100.5602FF% Reduction340.110.51760.050.79330.020.9139Pre-Cold T2*360.030.83550.030.84590.010.9382Multiple Regression ModelMultiple regression analysis was not conducted for T2* reduction since no significant relationship was found between this variable and any known covariates of BAT. Additionally, outdoor temperature was not associated with any BAT MR outcomes, and therefore, was not included as a covariate in any of the multiple regression models. While sex was not significantly associated with any of the BAT MR outcomes, this variable along with age were added to the models to account for biological differences between participants. Thus, multiple regression analyses were each conducted for the following BAT MR outcomes: pre-cold FF%, pre-cold T2* and FF% reduction. Age and sex were first added to the model (model 1) while body fat percentage was added last (model 2). Pre-Cold FF%As noted in Table 16, both multiple regression models were found to be significantly associated with pre-cold FF%. In both cases, sex was not found to be a significant correlate of pre-cold FF%. In the full model, both age and body fat percentage were found to be significant predictors of pre-cold FF%. The addition of body fat percentage in the model accounted for a significant increase in variance from 33.1% to 74.9%. Stepwise multiple regression analysis between pre-cold FF%, age, sex and body fat percentage Pre-Cold FF%VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant55.769 (4.142)< .0001*.331.002*Age (years).476 (.120).585< .0001*Sex (reference: male)1.148 (2.339).072.627Model 2Constant48.712 (2.759)< .0001*.749< .0001*Age (years).213 (.083).262.015 *Sex (reference: male)1.667 (1.458).105.261% Body Fat (%).533 (.074).726< .0001*Pre-Cold T2*As seen in Table 17, age and body fat percentage were found to significantly predict pre-cold T2* while sex did not add any significant predictive value. The addition of body fat percentage significantly increased the variance from 30.4% to 45.4%. For every increase in age of one year, T2* was 0.056 ms higher and for every 1% increase in body fat, T2* was 0.059 ms higher. Stepwise multiple regression analysis between pre-cold T2*, age, sex and body fat percentage Pre-Cold T2*VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant10.961 (.781)< .0001*.304.003*Age (years).085 (.023).562.001*Sex (reference: male).333 (.441).113.456Model 2Constant10.182 (.752)< .0001*.454< .0001 *Age (years).056 (.023).369.020*Sex (reference: male).390 (.398).133.334% Body Fat (%).059 (.020).434.007*FF% ReductionAs noted in Table 18, the first model, which included age and sex, was not found to be significantly associated with FF% reduction. In contrast, the inclusion of body fat percentage made the model statistically significant and was able to explain 42.9% of the variability in FF% reduction. Additionally, body fat percentage was found to be an independent predictor of FF% reduction. Stepwise multiple regression analysis between FF% reduction, age, sex and body fat percentageFF% Reduction VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant6.002 (1.618).001*.160.073Age (years)- .106 (.046)-.391.029*Sex (reference: male).209 (.929).038.824Model 2Constant7.893 (1.449)< .0001*.429.001 *Age (years)-.036 (.043)-.132.415Sex (reference: male).172 (.779).032.827% Body Fat (%)-.144 (.039)-.581.001*DiscussionAs previously stated in Chapter 1, it is important to note that when interpreting these findings, a lower FF% or T2* value are reflective of a browner phenotype while a higher FF% reduction (i.e. decrease in TG content) after cold exposure is indicative of BAT activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.22162", "ISBN" : "1053-1807", "ISSN" : "10531807", "PMID" : "20432356", "abstract" : "PURPOSE:To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).\\n\\nMATERIALS AND METHODS:Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.\\n\\nRESULTS:A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.\\n\\nCONCLUSION:Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nayak", "given" : "Krishna S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goran", "given" : "Michael I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagy", "given" : "Tim R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1195-1202", "title" : "Identification of brown adipose tissue in mice with fat-water IDEAL-MRI", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mri.2011.12.004", "ISBN" : "2122633255", "ISSN" : "0730725X", "PMID" : "22244539", "abstract" : "Purpose: The purpose was to compare T 2 * relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T 2 *-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T 2 * and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T 2 * and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Results: Significant differences (P<.01) in BAT T 2 * and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T 2 * and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T 2 * and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. Conclusion: T 2 * and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hines", "given" : "Catherine D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeder", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "323-329", "publisher" : "Elsevier Inc.", "title" : "Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.23531", "ISBN" : "1522-2586", "ISSN" : "10531807", "PMID" : "22180228", "abstract" : "We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tovar", "given" : "Jason P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavlova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "938-942", "title" : "Unequivocal identification of brown adipose tissue in a human infant", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^16,34,35", "plainTextFormattedCitation" : "16,34,35", "previouslyFormattedCitation" : "^16,34,35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,34,35. The main objective of this section was to examine if associations existed between BAT MR outcomes and known covariates of BAT including age, adiposity, sex and outdoor temperature. BAT and Age To date, a limited number of studies have examined the effects of age on BAT MR outcomes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-3", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^37,38,73", "plainTextFormattedCitation" : "37,38,73", "previouslyFormattedCitation" : "^37,38,72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38,73. Of note, these studies did not directly investigate the associations between age and BAT MR outcomes in the same population but only noted that their findings suggest that a relationship might exist. Additionally, no studies have investigated the effects of age on cold-stimulated BAT using MRI. As such, one of the primary objectives in this study was to determine if there was any relationship between BAT characteristics and activity with age. In this study, BAT characteristics (pre-cold FF% and pre-cold T2*) were positively correlated with age, while BAT activity (FF% reduction) was shown to have a negative correlation with age. These findings are consistent with the numerous studies that have shown a negative association between BAT mass and metabolic activity (as measured by 18F-FDG uptake) and age ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/oby.2010.105", "ISBN" : "1930-7381 (Print) 1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "20448535", "abstract" : "Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20\u201328 years underwent FDG-PET after 2-h cold exposure at 19 \u00b0C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 \u00b0C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 \u00b1 97 kcal/day, being comparable with that of the BAT-negative group (1,434 \u00b1 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 \u00b1 293 (P < 0.05) and slightly by 42 \u00b1 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 \u00b0C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 \u00b0C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "6" ] ] }, "page" : "13-16", "publisher" : "Nature Publishing Group", "title" : "Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/oby.20456", "ISBN" : "1930-739X (Electronic)\\r1930-7381 (Linking)", "ISSN" : "19307381", "PMID" : "23554353", "abstract" : "OBJECTIVE: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. DESIGN AND METHODS: Using positron emission tomography (PET), we quantified cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans. Further, cold-induced glucose uptake was measured in obese subjects before and after a five-month conventional weight loss. RESULTS: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. CONCLUSIONS: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.", "author" : [ { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noponen", "given" : "Tommi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viljanen", "given" : "Tapio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-6", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2279-2287", "title" : "Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1111/nyas.12195", "ISBN" : "1749-6632", "ISSN" : "00778923", "PMID" : "23909713", "abstract" : "The visualization of brown adipose tissue (BAT) in pediatric patients undergoing positron emission tomography/computed tomography (PET/CT) examinations is dependent on multiple physiologic and technical factors, such as age, sexual maturity, fat accumulation, disease status, medications, plasma glucose concentration, radiotracer dosage, acquisition parameters, and season and temperature during examinations. Evidence also suggests that children with metabolically active BAT have significantly greater muscle volume than those without visualized BAT, and that in both boys and girls, the amount of BAT increases during puberty. Hence, concurrent with the gains in skeletal muscle during infancy and puberty, all infants and adolescents have large amounts of BAT. New magnetic resonance imaging (MRI) techniques that discern the cytological differences between brown and white adipose tissue will likely provide the platform to reliably measure BAT in healthy subjects and determine the relevance of this tissue in humans.", "author" : [ { "dropping-particle" : "", "family" : "Ponrartana", "given" : "Skorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "24-29", "title" : "On the relevance of brown adipose tissue in children", "type" : "article-journal", "volume" : "1302" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1038/oby.2011.125", "ISBN" : "1930-7381 (Print)\\r1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "21566561", "abstract" : "Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 \u00b0C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-Ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-8", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "9", "12" ] ] }, "page" : "1755-1760", "publisher" : "Nature Publishing Group", "title" : "Age-Related Decrease in Cold-Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{5,6,11,18\u201320,23,24}", "plainTextFormattedCitation" : "5,6,11,18\u201320,23,24", "previouslyFormattedCitation" : "^{5,6,11,18\u201320,23,24}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,6,11,18–20,23,24. Findings in this study, further support the results reported by Franz et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷³", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "⁷²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73 where they found SCV BAT FF% to be significantly different between children and elderly adults. Additionally, Hu et al. reported significantly lower BAT FF% in infants compared to children ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^37,38", "plainTextFormattedCitation" : "37,38", "previouslyFormattedCitation" : "^37,38" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38. It is important to note that findings reported in this thesis were the first to show that BAT T2* signal and BAT activity (as measured by FF% reduction) also follow an age-dependent decline similar to pre-cold BAT FF%. Together these findings suggest that MRI can be utilized to detect differences in BAT associated with age irrespective of cold-activation. To summarize, findings in this study suggest that BAT MR characteristics and activity are negatively associated with age in adults between the ages of 18 and 50 years, similar to findings with 18F-FDG PET-CT and preliminary findings with MR. BAT and AdiposityAlthough there have been numerous research studies published that show an inverse association between BAT and measures of adiposity – these studies have mostly been limited to 18F-FDG PET-CT studies (see Chapter 1) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/db10-0004", "ISBN" : "1939-327X (Electronic)\\n0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "20357363", "abstract" : "OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.\\n\\nRESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.\\n\\nRESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09).\\n\\nCONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.", "author" : [ { "dropping-particle" : "", "family" : "Pfannenberg", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Matthias K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripkens", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stef", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deckert", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmadl", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimold", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "Hans Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claussen", "given" : "Claus D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefan", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7", "1" ] ] }, "page" : "1789-1793", "title" : "Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/oby.2010.105", "ISBN" : "1930-7381 (Print) 1930-7381 (Linking)", "ISSN" : "1930-7381", "PMID" : "20448535", "abstract" : "Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20\u201328 years underwent FDG-PET after 2-h cold exposure at 19 \u00b0C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 \u00b0C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 \u00b1 97 kcal/day, being comparable with that of the BAT-negative group (1,434 \u00b1 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 \u00b1 293 (P < 0.05) and slightly by 42 \u00b1 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 \u00b0C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 \u00b0C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.", "author" : [ { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aita", "given" : "Sayuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "6" ] ] }, "page" : "13-16", "publisher" : "Nature Publishing Group", "title" : "Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/oby.20456", "ISBN" : "1930-739X (Electronic)\\r1930-7381 (Linking)", "ISSN" : "19307381", "PMID" : "23554353", "abstract" : "OBJECTIVE: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. DESIGN AND METHODS: Using positron emission tomography (PET), we quantified cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans. Further, cold-induced glucose uptake was measured in obese subjects before and after a five-month conventional weight loss. RESULTS: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. CONCLUSIONS: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.", "author" : [ { "dropping-particle" : "", "family" : "Orava", "given" : "Janne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noponen", "given" : "Tommi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viljanen", "given" : "Tapio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enerb\u00e4ck", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-6", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2279-2287", "title" : "Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1056/NEJMoa0808718", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357405", "abstract" : "Background Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. Methods We studied 24 healthy men \u2014 10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], <25) and 14 who were overweight or obese (BMI, \u226525) \u2014 under thermoneutral conditions (22\u00b0C) and during mild cold exposure (16\u00b0C). Putative brown-adipose-tissue activity was ...", "author" : [ { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanhommerig", "given" : "Joost W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smulders", "given" : "Nanda M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossaerts", "given" : "Jamie M.A.F.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemerink", "given" : "Gerrit J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouvy", "given" : "Nicole D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teule", "given" : "G.J. Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-7", "issue" : "15", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1500-1508", "title" : "Cold-Activated Brown Adipose Tissue in Healthy Men", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1152/ajpendo.00298.2010", "ISBN" : "1522-1555 (Electronic)\\r0193-1849 (Linking)", "ISSN" : "0193-1849", "PMID" : "20606075", "abstract" : "Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5-10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 \u00b1 1 vs. 52 \u00b1 1 years, P < 0.001) and leaner (20.1 \u00b1 0.9 vs. 24.9 \u00b1 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 \u00b1 0.1 vs. 5.5 \u00b1 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 \u00b1 0.5 vs. 58.2 \u00b1 0.8 kg, P < 0.001 and 4.9 \u00b1 0.3 vs. 5.5 \u00b1 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenfield", "given" : "J. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "K. K. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulham", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Endocrinology and Metabolism", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "10", "1" ] ] }, "page" : "601-606", "title" : "A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans", "type" : "article-journal", "volume" : "299" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{5,6,11,17\u201321}", "plainTextFormattedCitation" : "5,6,11,17\u201321", "previouslyFormattedCitation" : "^{5,6,11,17\u201321}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,6,11,17–21. For example, Saito et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-0530.", "PMID" : "19401428", "author" : [ { "dropping-particle" : "", "family" : "Saito", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamatsu-ogura", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsushita", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Kumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoneshiro", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio-kobayashi", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwanaga", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kameya", "given" : "Toshimitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakada", "given" : "Kunihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Yuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsujisaki", "given" : "Masayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "JULY", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1526-1531", "title" : "High Incidence of Metabolically Active Brown Adipose Effects of Cold Exposure and Adiposity", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶", "plainTextFormattedCitation" : "6", "previouslyFormattedCitation" : "⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6 found 18F-FDG uptake to be inversely related to BMI (r = -0.67), total body fat (r = -0.56) and visceral fat (r = -0.68). In the current study, a very strong correlation existed between all BAT MR outcomes and adiposity. These results were consistent to the very limited studies that have used FF% and/or T2* to characterize BAT in participants with various body sizes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^38,68,74", "plainTextFormattedCitation" : "38,68,74", "previouslyFormattedCitation" : "^38,67,73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38,68,74. In children, Hu et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38 found a moderate inverse correlation between BMI percentile with both FF% and T2*. The same group found significantly higher FF% and T2* values in overweight/obese children when compared to normal weight individuals ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38. Interestingly, large MRI studies that have examined the relationship between BAT MR outcomes and adiposity were in children, most likely due to the limitation of enrolling this population in PET-CT studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^38,68,74", "plainTextFormattedCitation" : "38,68,74", "previouslyFormattedCitation" : "^38,67,73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38,68,74. Furthermore, no MRI studies have been conducted to assess the relationship between cold-activated BAT and adiposity. Findings reported in this thesis show for the first time that BAT activity as measured by MR FF% reduction, is negatively associated with adiposity. Taken together, there is strong evidence to suggest that BAT MR outcomes are closely associated with adiposity, consistent with previous 18F-FDG PET-CT studies. BAT and SexAs previously described in Chapter 1, it is currently unclear if there is any relationship between BAT and sex due to conflicting results in the literature ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db10-0004", "ISBN" : "1939-327X (Electronic)\\n0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "20357363", "abstract" : "OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.\\n\\nRESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.\\n\\nRESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09).\\n\\nCONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.", "author" : [ { "dropping-particle" : "", "family" : "Pfannenberg", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Matthias K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripkens", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stef", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deckert", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmadl", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimold", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "Hans Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claussen", "given" : "Claus D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefan", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7", "1" ] ] }, "page" : "1789-1793", "title" : "Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1172/JCI68993", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738", "PMID" : "23867626", "abstract" : "In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show \"browning\" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "Anouk A J J", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeks", "given" : "Joris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "Boudewijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vijgen", "given" : "Guy H E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visser", "given" : "Mari\u00eblle G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "Maarten J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f6rgensen", "given" : "Johanna A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottaghy", "given" : "Felix M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "Wouter D.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Investigation", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8", "1" ] ] }, "page" : "3395-3403", "title" : "Cold acclimation recruits human brown fat and increases nonshivering thermogenesis", "type" : "article-journal", "volume" : "123" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1073/pnas.1207911109", "ISBN" : "0027-8424", "ISSN" : "0027-8424", "PMID" : "22665804", "abstract" : "As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "A. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Y.-C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sze", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "English", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holman", "given" : "A. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "M. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "G. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences", "id" : "ITEM-4", "issue" : "25", "issued" : { "date-parts" : [ [ "2012", "6", "19" ] ] }, "page" : "10001-10005", "publisher" : "National Academy of Sciences", "title" : "Cold but not sympathomimetics activates human brown adipose tissue in vivo", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^5,17,26,27", "plainTextFormattedCitation" : "5,17,26,27", "previouslyFormattedCitation" : "^5,17,26,27" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,17,26,27. To date, no studies have directly investigated the role of sex with BAT outcomes as measured using MRI. In this study, BAT MR outcomes were not found to be significantly different between males and females. This finding is consistent with previous reports that showed BAT prevalence is similar between males and females in cold-activated BAT studies (via 18F-FDG PET-CT) that used a direct-to-skin cooling delivery method ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI68993", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738", "PMID" : "23867626", "abstract" : "In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show \"browning\" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. 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In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "A. 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R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences", "id" : "ITEM-2", "issue" : "25", "issued" : { "date-parts" : [ [ "2012", "6", "19" ] ] }, "page" : "10001-10005", "publisher" : "National Academy of Sciences", "title" : "Cold but not sympathomimetics activates human brown adipose tissue in vivo", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^26,27", "plainTextFormattedCitation" : "26,27", "previouslyFormattedCitation" : "^26,27" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26,27. The lack of relationship between BAT MR outcomes and sex may be explained by the specific cold exposure protocol used in the study and the careful control of hormone fluctuations in female participants. It has been suggested that previous 18F-FDG PET-CT findings that reported a relationship between BAT activity and sex were limited to non-cold stimulated and air-cooling studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db10-0004", "ISBN" : "1939-327X (Electronic)\\n0012-1797 (Linking)", "ISSN" : "00121797", "PMID" : "20357363", "abstract" : "OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.\\n\\nRESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.\\n\\nRESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09).\\n\\nCONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.", "author" : [ { "dropping-particle" : "", "family" : "Pfannenberg", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Matthias K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripkens", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stef", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deckert", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmadl", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimold", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "Hans Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claussen", "given" : "Claus D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefan", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7", "1" ] ] }, "page" : "1789-1793", "title" : "Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1152/ajpregu.00021.2014", "ISBN" : "1522-1490 (Electronic)\\r0363-6119 (Linking)", "ISSN" : "0363-6119", "PMID" : "24871967", "abstract" : "The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the \u201cfixed volume\u201d methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "A. A. J. J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierts", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "W. D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Regulatory, Integrative and Comparative Physiology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "103-113", "title" : "Cold-activated brown adipose tissue in human adults: methodological issues", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^5,17,25", "plainTextFormattedCitation" : "5,17,25", "previouslyFormattedCitation" : "^5,17,25" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,17,25, primarily due to the difference in thermal sensation between sexes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpregu.00021.2014", "ISBN" : "1522-1490 (Electronic)\\r0363-6119 (Linking)", "ISSN" : "0363-6119", "PMID" : "24871967", "abstract" : "The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the \u201cfixed volume\u201d methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "A. A. J. J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierts", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "W. D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Regulatory, Integrative and Comparative Physiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "103-113", "title" : "Cold-activated brown adipose tissue in human adults: methodological issues", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s004240050690", "ISBN" : "0031-6768 (Print)\\r0031-6768 (Linking)", "ISSN" : "00316768", "PMID" : "9716701", "abstract" : "The effects of acute and chronic acclimation to cold on uncoupling protein 1 (UCP1) levels, as well as on GDP-binding to mitochondria, cytochrome c oxidase activity and mitochondrial protein concentration in brown adipose tissue (BAT) of intact male and female rats have been analyzed. Results reveal that females rats are more sensitive to cold because their threshold temperature for the thermogenic response is set at a higher value (around 22 degreesC) than that of males (around 18 degreesC), hence leading to differences in BAT UCP1 levels between the sexes at different environmental temperatures. In vitro experiments showed that steroid hormones, beta-estradiol, estrone and progesterone, can reduce norepinephrine-induced UCP1 synthesis in brown adipocytes differentiated in primary culture. Thus the different sex-associated response of cold-induced thermogenesis in rats does not appear to be explained by a direct action of sex steroids upon the adipocyte, implying that other factors in the thermogenic regulatory system must be involved.", "author" : [ { "dropping-particle" : "", "family" : "Quevedo", "given" : "Santiago", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roca", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pic\u00f3", "given" : "Catalina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palou", "given" : "Andreu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pflugers Archiv European Journal of Physiology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "689-695", "title" : "Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue", "type" : "article-journal", "volume" : "436" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^25,91", "plainTextFormattedCitation" : "25,91", "previouslyFormattedCitation" : "^25,91" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }25,91. As previously noted in Part 1, the amount of cold exposure delivered to all participants was found to be consistent irrespective of body size or sex. Thus, the consistent amount of cold exposure delivered in this study might explain the lack of relationship between BAT MR outcomes and sex. Of note, these findings further support the robustness and consistency of the cold exposure protocol used in this study. In rodents, sex hormones such as estradiol and progesterone have been shown to have an inhibitory effect on BAT thermogenesis, although no studies in humans have directly confirmed this finding ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0008-4212 (Print)", "ISSN" : "00084212", "PMID" : "8143246", "abstract" : "High plasma levels of estradiol are known to reduce the GDP binding of brown adipose tissue. Since GDP binding depends on the level of sympathetic discharge to brown adipose tissue, we measured the responsiveness to noradrenaline of brown adipocytes isolated from female rats with high plasma levels of estradiol. Noradrenaline responsiveness was assessed by measuring the respiration rate of isolated brown adipocytes in the presence of different concentrations of noradrenaline. Both control and treated adipocytes showed the same basal respiratory rate (27 +/- 6 and 24 +/- 4 nmol O2.min-1.10(-6) cells, respectively). The presence of noradrenaline (0.1, 1, and 10 microM) in the medium increased the respiration rate of both kinds of adipocytes in a dose-dependent manner. However, the response was markedly reduced in adipocytes isolated from estradiol-treated rats. These results suggest that estradiol impairs the responsiveness of brown adipose tissue to the sympathetic nervous system. Three possible mechanisms are suggested as accounting for the observed decreased responsiveness to noradrenaline, i.e., a direct action of estradiol in brown adipocytes, a modulatory role of estradiol in the central control of the sympathetic discharge to brown adipose tissue, and the interference of catecholestrogens with noradrenaline synthesis at the sympathetic terminals.", "author" : [ { "dropping-particle" : "", "family" : "Puerta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abelenda", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fernandez", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Can J Physiol Pharmacol", "id" : "ITEM-1", "issue" : "10-11", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "858-861", "title" : "Reduced noradrenaline responsiveness of brown adipocytes isolated from estradiol-treated rats", "type" : "article-journal", "volume" : "71" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s004240050690", "ISBN" : "0031-6768 (Print)\\r0031-6768 (Linking)", "ISSN" : "00316768", "PMID" : "9716701", "abstract" : "The effects of acute and chronic acclimation to cold on uncoupling protein 1 (UCP1) levels, as well as on GDP-binding to mitochondria, cytochrome c oxidase activity and mitochondrial protein concentration in brown adipose tissue (BAT) of intact male and female rats have been analyzed. Results reveal that females rats are more sensitive to cold because their threshold temperature for the thermogenic response is set at a higher value (around 22 degreesC) than that of males (around 18 degreesC), hence leading to differences in BAT UCP1 levels between the sexes at different environmental temperatures. In vitro experiments showed that steroid hormones, beta-estradiol, estrone and progesterone, can reduce norepinephrine-induced UCP1 synthesis in brown adipocytes differentiated in primary culture. Thus the different sex-associated response of cold-induced thermogenesis in rats does not appear to be explained by a direct action of sex steroids upon the adipocyte, implying that other factors in the thermogenic regulatory system must be involved.", "author" : [ { "dropping-particle" : "", "family" : "Quevedo", "given" : "Santiago", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roca", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pic\u00f3", "given" : "Catalina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palou", "given" : "Andreu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pflugers Archiv European Journal of Physiology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "689-695", "title" : "Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue", "type" : "article-journal", "volume" : "436" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^91,93", "plainTextFormattedCitation" : "91,93", "previouslyFormattedCitation" : "^91,93" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }91,93. In this study, the second visit (i.e. MRI measurement of BAT) was conducted within seven days of the start of menstruation (follicular phase) in female participants, which is when estrogen and progesterone levels were predicted to be at their lowest point ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/cphy.c130029", "ISBN" : "2040-4603 (Electronic)\\r2040-4603 (Linking)", "ISSN" : "20404603", "PMID" : "24715568", "abstract" : "The present discussion reviews current knowledge regarding influences of the primary reproductive hormones on mechanisms of thermoregulatory control in women. The human body is remarkably capable of maintaining body temperature within a few tenths of a degree of normal (37\u00b0C) over a wide range of activity and environmental exposures; this regulation is accomplished via integration of central and peripheral thermal information at the preoptic area of the anterior hypothalamus (PO/AH). We describe both central and peripheral mechanisms involved in controlling thermoregulation in humans, and how these mechanisms are affected by sex and hormone exposure. Estrogens generally promote vasodilation, heat dissipation, and lower body temperature and progesterone or progestins generally have the opposite effect. Estrogens and progesterone/progestins can also interact with androgens; this is an important point because androgens in the body can increase in both older and younger women. The study of reproductive hormone (estrogens, progesterone, luteinizing, and follicle stimulating hormones) effects on body systems is challenging because of the complex and multifaceted influences of these hormones, both individually and in combination. Thus, a number of methods to alter hormone exposure are explained in this article. We conclude that men and women do not exhibit major quantitative differences in physiological thermoregulatory responses to exercise and/or body heating when factors such as fitness and body size are taken into account. However, female and male reproductive hormones have important influences that can significantly alter individual thermoregulatory responses at various points throughout the lifespan.", "author" : [ { "dropping-particle" : "", "family" : "Charkoudian", "given" : "Nisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stachenfeld", "given" : "Nina S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Comprehensive Physiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "3", "19" ] ] }, "page" : "793-804", "publisher" : "John Wiley & Sons, Inc.", "publisher-place" : "Hoboken, NJ, USA", "title" : "Reproductive hormone influences on thermoregulation in women", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁵", "plainTextFormattedCitation" : "65", "previouslyFormattedCitation" : "⁶⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }65. Given that previous studies did not account for hormone fluctuations in female subjects, it is possible that these fluctuations might have confounded BAT outcomes. Although, the effects of hormone fluctuations and cold exposure on BAT outcomes cannot be dissociated in this study, findings in the literature provide strong evidence that hormone fluctuations should be accounted for during BAT measurements. BAT and Outdoor Temperature In this study, outdoor temperature was not found to be associated with either BAT characteristics or activity. This contrasts with findings reported in several 18F-FDG PET-CT retrospective studies that showed an inverse relationship between outdoor temperature and BAT outcomes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2010-0989", "ISBN" : "1945-7197 (Electronic)\\r0021-972X (Linking)", "ISSN" : "0021972X", "PMID" : "20943785", "abstract" : "CONTEXT In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age \u00d7 sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Routhier-Labadie", "given" : "Annick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellemare", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhal-Chaieb", "given" : "Lajmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "192-199", "title" : "Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1100/2012/793039", "ISBN" : "1537-744X (Electronic)\\n1537-744X (Linking)", "ISSN" : "1537-744X", "PMID" : "22593707", "abstract" : "<p> Brown adipose tissue (BAT) is important for regulating body weight. Environmental temperature influences BAT activation. Activated BAT is identifiable using <math> <mrow> <mtext>F</mtext> <mrow> <mn>18</mn> </mrow> </mrow> </math> -fluorodeoxyglucose positron emission tomography/computed tomography ( <math> <mrow> <mtext>F</mtext> <mrow> <mn>18</mn> </mrow> </mrow> </math> -FDG PET/CT). <math> <mrow> <mtext>F</mtext> <mrow> <mn>18</mn> </mrow> </mrow> </math> -FDG PET/CT scans done between June 2005 and May 2009 in our institution in tropical southern Taiwan and BAT studies from PubMed (2002\u20132011) were reviewed, and the average outdoor temperatures during the study periods were obtained. A simple linear regression was used to analyze the association between the prevalence of activated BAT ( <math> <mi>P</mi> </math> ) and the average outdoor temperature ( <math> <mi>T</mi> </math> ). The review analysis for 9 BAT studies ( <math> <mi>n</mi> <mo>=</mo> <mn>16</mn> <mo>,</mo> <mn>765</mn> </math> ) showed a significant negative correlation ( <math> <mi>r</mi> <mo>=</mo> <mo>-</mo> <mn>0.741</mn> </math> , <math> <mi>P</mi> <mo>=</mo> <mn>0.022</mn> </math> ) between the prevalence of activated BAT and the average outdoor temperature. The equation of the regression line is <math> <mi>P</mi> <mrow> <mo>(</mo> <mo>%</mo> <mo>)</mo> </mrow> <mo>=</mo> <mn>6.99</mn> <mo>\u2212</mo> <mn>0.20</mn> <mo>\u00d7</mo> <mi>T</mi> <mrow> <mo>\u2009\u2009(</mo> <mrow> <mtext>C</mtext> <mo>\u2218</mo> </mrow> <mo>)</mo> </mrow> </math> . The prevalence of activated BAT decreased by 1% for each <math> <mn>5</mn> <mtext>C</mtext> <mo>\u2218</mo> </math> increase in average outdoor temperature. In a neutral ambient temperature, the prevalence of activated BAT is low and especially rare in the tropics. There is a significant linear negative correlation between the prevalence of activated BAT and the average outdoor temperature. </p>", "author" : [ { "dropping-particle" : "", "family" : "Huang", "given" : "Yung-Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsu", "given" : "Chien-Chin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Pei-Wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yen-Hsiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Tai-Been", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Bi-Fang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiu", "given" : "Nan-Tsing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Scientific World Journal", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-6", "title" : "Review Analysis of the Association between the Prevalence of Activated Brown Adipose Tissue and Outdoor Temperature", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cohade", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mourtzikos", "given" : "Karen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahl", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of nuclear medicine", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "1267-1270", "publisher" : "Society of Nuclear Medicine", "title" : "\u201cUSA-Fat\u201d: Prevalence Is Related to Ambient Outdoor Temperature\u2014Evaluation with 18F-FDG PET/CT", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1056/NEJMoa0810780", "ISBN" : "1533-4406 (Electronic)\\n0028-4793 (Linking)", "ISSN" : "0028-4793", "PMID" : "19357406", "abstract" : "Background Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET\u2013CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from t...", "author" : [ { "dropping-particle" : "", "family" : "Cypess", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Sanaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gethin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tal", "given" : "Ilan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodman", "given" : "Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldfine", "given" : "Allison B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Frank C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Edwin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Yu-Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doria", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolodny", "given" : "Gerald M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "C. Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-4", "issue" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "9" ] ] }, "page" : "1509-1517", "title" : "Identification and Importance of Brown Adipose Tissue in Adult Humans", "type" : "article-journal", "volume" : "360" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^5,18,94,95", "plainTextFormattedCitation" : "5,18,94,95", "previouslyFormattedCitation" : "^5,18,94,95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5,18,94,95. Given the retrospective nature of these studies, BAT measurements did not include either an acclimatization period or a cold treatment to stimulate BAT activity. Thus, the higher rates of BAT detection associated with decreased outdoor temperature in these studies could have been due to either previously activated BAT or inadequate cold exposure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpregu.00021.2014", "ISBN" : "1522-1490 (Electronic)\\r0363-6119 (Linking)", "ISSN" : "0363-6119", "PMID" : "24871967", "abstract" : "The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the \u201cfixed volume\u201d methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.", "author" : [ { "dropping-particle" : "", "family" : "Lans", "given" : "A. A. J. J.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierts", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vosselman", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrauwen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brans", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marken Lichtenbelt", "given" : "W. D.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJP: Regulatory, Integrative and Comparative Physiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "103-113", "title" : "Cold-activated brown adipose tissue in human adults: methodological issues", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "²⁵" }, "properties" : { "noteIndex" : 93 }, "schema" : "" }25. In this study, participants were subjected to a 30-minute acclimatization phase at room temperature to ensure that all participants were at thermoneutrality prior to pre-cold BAT MRI measurements. Additionally, a consistent and standardized cold exposure protocol was delivered to all participants. These considerations in the study protocol potentially explain the lack of relationship between BAT MR outcomes and outdoor temperature in this study. Results of this study agree with recent findings reported by Haq et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/s41598-017-11537-x", "ISSN" : "2045-2322", "abstract" : "The discovery of brown adipose tissue (BAT) in adults has sparked interest in its role as a therapeutic target in metabolic disorders. Infrared thermography is a promising way to quantify BAT; however, a standardized methodology has not been established. This study aims to establish a standardized and reproducible protocol to measure thermal response to cold in the supraclavicular area using thermographic imaging. In Phase 1, we compared the thermal response to 12 \u00b0C cold after acclimation at either 32 \u00b0C or room temperature using thermographic imaging. Repeatability of the 32 \u00b0C acclimation trial was studied in a second group in Phase 2. Phase 1 included 28 men (mean age 23.9 \u00b1 5.9 y; mean BMI 25.2 \u00b1 3.9 kg/m2) and Phase 2 included 14 men (mean age 20.9 \u00b1 2.4 y; mean BMI 23.6 \u00b1 3.1 kg/m2). The thermal response was greater after 32 \u00b0C than after room temperature acclimation (0.22 \u00b1 0.19 vs 0.13 \u00b1 0.17 \u00b0C, p = 0.05), was not related to outdoor temperature (r = \u22120.35, p = 0.07), did not correlate with supraclavicular fat (r = \u22120.26, p = 0.21) measured with dual-energy x-ray absorptiometry and was repeatable [ICC 0.69 (0.14\u20130.72)]. Acclimation at 32 \u00b0C followed by cold generates a reproducible change in supraclavicular skin temperature measurable by thermal imaging that may be indicative of BAT metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Haq", "given" : "Tahniyah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crane", "given" : "Justin D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanji", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gunn", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinberg", "given" : "Gregory R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scientific Reports", "id" : "ITEM-1", "issue" : "11934", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "publisher" : "Springer US", "title" : "Optimizing the methodology for measuring supraclavicular skin temperature using infrared thermography; implications for measuring brown adipose tissue activity in humans", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁸", "plainTextFormattedCitation" : "28", "previouslyFormattedCitation" : "²⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28 wherein following an acclimatization phase of one hour at room temperature, no associations were found between BAT activity (as measured by infrared thermography) and outdoor temperature. Multiple Regression Model As previously noted, most BAT MR studies have been limited in terms of their sample size and population sample. As such, the majority of these studies did not have enough power to assess the effects of each covariate on BAT MR outcomes in a multivariate model ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-8", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-9", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-10", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-11", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-12", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{37,38,66\u201374,44}", "plainTextFormattedCitation" : "37,38,66\u201374,44", "previouslyFormattedCitation" : "^{37,38,65\u201374}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37,38,66–74,44. Multiple stepwise regression analyses were conducted in this study to better understand how each covariate affected BAT characteristics (pre-cold FF% or pre-cold T2*) and BAT activity (FF% reduction). Age and sex were first added to the model, followed by body fat percentage. This specific order was chosen to first evaluate the effects of age and sex on each BAT MR outcome, before accounting for body fat percentage which has been previously shown to have a strong correlation with all BAT MR outcomes. With only age and sex in the model, age was found to be a significant predictor for both pre-cold BAT MR outcomes but the model only tended to be significant for FF% reduction (p = 0.073). This may be attributable to the inherent variability in cold response and the limited age distribution (i.e. more younger individuals) between participants in the current study. The inclusion of body fat percentage to the final model not only resulted in a significant increase in variance for all regression analyses but was also able to significantly predict each of the BAT MR outcome. Based on these findings, body fat percentage may play a larger role in defining BAT MR outcomes when compared to age. Interpretation of BAT MR OutcomesAn in-depth comparison of BAT MR outcomes is presented in Appendix Section 7.2.5 Table A15; pp 134-135. In that table, the mechanism, advantages and limitations of each BAT MR outcome as well as their associations with known covariates are outlined. The importance of intracellular TG lipolysis in its role during BAT activation has been extensively investigated. It has been suggested that BAT primarily uses endogenous FFA as its main source of energy during activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1139/y86-101", "ISBN" : "0030229505338", "ISSN" : "0008-4212", "PMID" : "3730946", "abstract" : "The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 mumol/min) and release of glycerol (0.9 and 1.2 mumol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 mumol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation.(ABSTRACT TRUNCATED AT 250 WORDS)", "author" : [ { "dropping-particle" : "", "family" : "Ma", "given" : "Stephanie W. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foster", "given" : "David O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian Journal of Physiology and Pharmacology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1986", "5" ] ] }, "page" : "609-614", "title" : "Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue <i>in vivo</i>", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1152/physrev.00015.2003", "ISBN" : "0031-9333 (Print) 0031-9333 (Linking)", "ISSN" : "0031-9333", "PMID" : "14715917", "abstract" : "The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.", "author" : [ { "dropping-particle" : "", "family" : "Cannon", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedergaard", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiological Reviews", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "277-359", "title" : "Brown Adipose Tissue: Function and Physiological Significance", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^4,30,31", "plainTextFormattedCitation" : "4,30,31", "previouslyFormattedCitation" : "^4,30,31" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4,30,31. Recently, Blondin et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2016.12.005", "ISSN" : "19327420", "PMID" : "28089568", "abstract" : "Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "438-447", "title" : "Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁵", "plainTextFormattedCitation" : "75", "previouslyFormattedCitation" : "⁷⁵" }, "properties" : { "noteIndex" : 89 }, "schema" : "" }75 showed that BAT activity in adult humans is dependent on intracellular TG lipolysis as the inhibition of this pathway abolished cold-induced BAT thermogenesis. Additionally, with the use of PET tracers, the contribution of substrate uptake during BAT activity has been shown to be minimal ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ncomms14146", "ISSN" : "2041-1723", "PMID" : "28134339", "abstract" : "In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 \u00b0C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid ((18)FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.", "author" : [ { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tingelstad", "given" : "Hans C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noll", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frisch", "given" : "Fr\u00e9d\u00e9rique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "\u00c9ric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Communications", "id" : "ITEM-1", "issue" : "14146", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-9", "title" : "Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1172/JCI60433DS1", "ISBN" : "1558-8238 (Electronic)\\r0021-9738 (Linking)", "ISSN" : "00219738 15588238", "PMID" : "22269323", "author" : [ { "dropping-particle" : "", "family" : "Ouellet", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labb\u00e9", "given" : "S\u00e9bastien M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blondin", "given" : "Denis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phoenix", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu\u00e9rin", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haman", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turcotte", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richard", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentier", "given" : "Andr\u00e9 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical investigation", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "545-552", "title" : "Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans", "type" : "article-journal", "volume" : "122" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^31,76", "plainTextFormattedCitation" : "31,76", "previouslyFormattedCitation" : "^31,76" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,76. Based on findings in the literature, there is much evidence to suggest that quantifying the change in TG content after cold exposure is the best measure of BAT activity. This notion is extended in the current study where the use of MRI in detecting BAT was not only able to detect extreme changes in FF% signals after cold exposure but was also found to be very reliable between raters. Additionally, the decline in TG content (as measured by FF% reduction) after cold exposure was specific to the SCV region, as this decline was not demonstrated in the posterior neck fat. Altogether, these findings provide strong evidence that measuring the change in TG content (i.e. FF% reduction) after cold exposure is the most appropriate single independent measure of BAT activity. examination of the relationship between bat (characteristicS and activity) and liver fat (OBJECTIVE 3)BACKGROUNDAs previously described in Chapter 1, the relationship between BAT and NAFLD has not been extensively investigated in humans. To date, only two non-cold stimulated 18F-FDG studies have assessed the association between BAT and liver fat ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59. In these studies, the researchers found that individuals with detectable BAT activity not only had lower NAFLD prevalence but also better hepatic function ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59. However, these studies were limited by their population sample (i.e. referred from oncology clinics) and its retrospective design (i.e. measurement of non-cold stimulated BAT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59. Due to these limitations, the applicability of these results to healthy humans remains uncertain. As such, the primary objective of this chapter was to examine the relationship between BAT MR outcomes and liver fat before and after adjusting for potential covariates including age, sex and body fat percentage. As previously described in Chapter 1, liver fat is inversely associated with body fat percentage, while the relationship between liver fat and age and sex remains uncertain. METHODSPrimary OutcomeLiver FatIn this study, liver MRI scans were acquired in the axial plane using a 32-channel torso array coil. These scans were conducted in a breath-hold (approximately 17 seconds) as previous protocol trials have showed that breathing introduces considerable motion artefacts. A multi-slice segmentation was performed to ensure that the entire liver was included in the analysis. ROIs were drawn over the entire liver using “smart trace”, a tool that “snaps” to the edges of regions where changes in voxel intensities are high. The water-related image was used as a reference when the boundaries of the liver were not clearly defined in the fat-fraction image (see Figure 17). The ROIs were then post-processed using a 2D 3x3 erode (jack structural element) to correct for partial volume effects. It is important to note that the number of slices included in the segmentation of the liver is dependent on its size. Fat fraction map (left) and water-related image (right) of the liver. Exposure Outcome As previously described in Part 1, MRI was used to measure BAT characteristics and activity in the SCV region. BAT characteristics were defined as MR outcomes before the cold exposure treatment (i.e. pre-cold FF% or pre-cold T2*). Additionally, BAT activity was defined as the decrease in FF% (FF% reduction) in the SCV after cold exposure. * For detailed methodology on BAT MR Outcomes – refer to Section 3.3.2; pp 30Potential CovariatesFactors that are known to be associated with liver fat include age, sex and body fat percentage. Both age and sex were self-reported. Body fat percentage was measured using a DEXA scanner (for detailed methodology – refer to Section 3.7.2; pp 46).Statistical AnalysisParticipant Demographics Participant demographics were presented as n or n (%) for categorical variables and mean (SD) or median [Q1, Q3] for skewed variables. Normality was tested using Shapiro-Wilk W-test which is designed for small sample sizes (n ≤ 50). Data that did not follow a normal distribution were either log- or square root-transformed and re-tested for normality. If the data failed to conform to a normal distribution following transformation, non-parametric tests were used for analyses. A scatter plot was used to assess the linearity of relationships. Relationship between BAT and Liver Fat Given that liver fat was non-normally distributed, a Spearman’s rank correlation coefficient was used to determine the relationship between each BAT MR outcome (i.e. pre-cold FF%, pre-cold T2* and FF% reduction) and liver fat. Multiple Regression Model Multivariate modelling was used to examine predictors or contributors to liver fat. Potential covariates of liver fat include age, sex and body fat percentage while each BAT MR measure was examined independently as an exposure outcome. The sample size was determined using the “rule of thumb” of 10 SPV ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.20982/tqmp.03.2.p043", "ISBN" : "1913-4126", "ISSN" : "1913-4126", "abstract" : "This article addresses the definition of power and its relationship to Type I and Type II errors. We discuss the relationship of sample size and power. Finally, we offer statistical rules of thumb guiding the selection of sample sizes large enough for sufficient power to detecting differences, associations, chi\u2010square, and factor analyses.", "author" : [ { "dropping-particle" : "", "family" : "Wilson Van Voorhis", "given" : "Carmen R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Betsy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Tutorials in Quantitative Methods for Psychology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "43-50", "title" : "Understanding Power and Rules of Thumb for Determining Sample Sizes", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹²", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "⁹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92. Therefore, approximately 40 participants were needed to have enough power to assess the potential relationship between BAT, age, sex and body fat percentage and liver fat. Since recruitment for the study is still ongoing, an interim analysis of 36 participants was presented in this thesis. Simple regression analysis was first conducted to determine the relationship between liver fat and potential covariates. Stepwise multiple regression analyses were then conducted to assess the relationship between each BAT MR outcome and liver fat while accounting for potential covariates. Both age and sex were first added to the model (model 1) followed by BAT MR outcome (either pre-cold FF%, pre-cold T2* or FF% reduction – model 2) while body fat percentage was added last (model 3). This specific order was chosen to evaluate the effects of BAT characteristics or activity on liver fat while first accounting for age and sex. Body fat percentage was added last to determine if the relationship between BAT and liver fat was related to adiposity (see Chapter 4).RESULTSParticipant Demographics Since the study is still ongoing, data from 36 participants was used to assess the relationship between BAT MR outcomes and liver fat (see Table 19). It is important to note that liver fat data was not collected for one participant due to limitations of the MRI scanner (i.e. did not fit in the scanner).Participant Demographics (Objective 3)Variable Name (units)N (%)Mean (SD) or Median [Q1, Q3]Min, MaxAge (years)3624.78 [22.73, 31.02]18.96, 57.5018-2925 (69.44)23.59 [21.93, 25.37]18.96, 28.0430-408 (22.22)36.20 [31.19, 40.13]30.56, 40.38≥ 413 (8.33)50.1149.56, 57.50SexMale23 (63.9)--Female13 (36.1)--Weight (kg)3672.27 [61.10, 87.13]50.80, 130.87Height (cm)36173.38 (9.17)158.07, 198.93BMI (kg/m2)3623.60 [21.60, 29.10]18.2, 44.0Underweight/Normal 2322.10 [20.90, 23.50]18.2, 24.9Overweight/Obese1330.40 [27.95, 33.55]25.4, 44.0Waist Circumference (cm)3680.72 [73.17, 95.13]62.17, 121.73Body Fat (%)3526.59 (10.41)11.7, 47.7Fat Mass (kg)3516.53 [11.19, 31.49]7.12, 45.65Lean Mass (kg)3551.92 (9.25)33.33, 67.86Pre-Cold FF (%)3670.47 (7.93)52.75, 84.82Post-Cold FF (%)3467.78 (10.12)47.94, 86.62FF% Reduction (%)342.97 (2.71)-1.80, 9.86Pre-Cold T2* (ms)3613.66 (1.46)10.68, 16.39Post-Cold T2* (ms)3412.93 (1.74)9.44, 16.72T2* Reduction (ms)340.84 (0.90)-1.10, 3.33Liver Fat (%)356.26 (3.77)3.41, 20.16Relationship between BAT and Liver Fat As previously noted in Chapter 4, T2* reduction was not deemed to be a good measure of BAT activity due to limitations in the study methodology. Thus, statistical analysis to assess the relationship between T2* reduction and liver fat was not conducted. In evaluating the relationship between BAT characteristics and liver fat, a moderate positive correlation was found between pre-cold FF% and liver fat (r = 0.60; p < 0.0001*) as with pre-cold T2* and liver fat (r = 0.47; p = 0.0040*) (see Figure 18). BAT MR characteristics and liver fatBAT activity (as measured by FF% reduction) was negatively correlated with liver fat (r = -0.38; p = 0.0295*) (see Figure 19). As seen in Figures 18-19, the relationship between BAT MR outcomes and liver fat seems to be driven by participants with high liver fat (i.e. little relationship in individuals with lower liver fat content). FF% reduction and liver fatMultiple Regression Model A simple regression analysis was first conducted to assess the relationship between liver fat and its covariates. Liver fat was found to be significantly correlated with both age and body fat percentage while sex was not significantly associated (see Table 20). Simple regression analysis between liver fat content and its covariatesVariable (units)Mean (SD) or FrequencyUnstd β (SE)R2p-valueAge (years)28.61 (9.66).139 (.065).120.041*Sex (reference: male)23M/13F1.527 (1.337).038.262Body Fat (%)26.83 (10.51).181 (.055).249.002*While sex was not significantly associated with liver fat, this variable along with age were added to the models to account for biological differences between participants. Thus, multiple regression analyses were each conducted to assess the potential relationship between liver fat and the following BAT MR outcomes (pre-cold FF%, pre-cold T2* or FF% reduction). Age and sex were first added to the model (model 1) followed by a BAT MR outcome (model 2) while body fat percentage was added last (model 3). The values presented in Table 21, was identical in each multiple regression analysis conducted for BAT MR outcomes since the first model only incorporated the relationship of liver fat with age and sex. Thus, to avoid redundancy, the results for the first model were described in this section. In model 1, age was found to be a significant correlate of liver fat while sex was not significantly associated.Relationship between liver fat with age and sex VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant.336 (2.245).882.191.034*Age.160 (.065).398.020*Sex (reference: male)2.115 (1.268).270.105Pre-Cold FF% and Liver Fat %As seen in Table 22, all models were found to be significantly associated with liver fat. In all cases, sex was not found to be a significant correlate of liver fat. In model 2, only pre-cold FF% was found to be a significant predictor of liver fat. Additionally, the inclusion of pre-cold FF% in the model significantly increased the variance from 19.1% to 35.8%. In the full model, no variables were found to have a significant predictive value to liver fat and only increased the variance by 1.5 % from the previous model. Stepwise multiple regression analysis between liver fat, age, sex, pre-cold FF% and body fat percentage Model A: Pre-Cold FF% and Liver Fat %VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant.336 (2.245).882.191.034*Age.160 (.065).398.020*Sex (reference: male)2.115 (1.268).270.105Model 2Constant-13.421 (5.245).016.358.003*Age.042 (.072).105.561Sex (reference: male)1.831 (1.152).234.122Pre-Cold FF%.247 (.087).500.008*Model 3Constant-9.246 (7.264).213.373.006*Age.047 (.072).118.517Sex (reference: male)2.017 (1.178).258.097Pre-Cold FF%.153 (.142).310.291% Body Fat.080 (.096).221.410Pre-Cold T2* and Liver Fat %As noted in Table 23, all regression models were found to be significantly associated with liver fat. In all models, sex and pre-cold T2* were not found to significantly predict liver fat. Additionally, the inclusion of pre-cold T2* in the model increased the explained variance from 19.1% to 23.6% while the subsequent addition of body fat percentage increased the explained variance by 11.4%. In the final model, body fat percentage was the only variable that could independently predict liver fat.Stepwise multiple regression analysis between liver fat content, age, sex, pre-cold T2* and % body fat.Model B: Pre-Cold T2* and Liver Fat %VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant.336 (2.245).882.191.034*Age.160 (.065).398.020*Sex (reference: male)2.115 (1.268).270.105Model 2Constant-7.166 (5.928).236.236.037*Age.102 (.077).253.196Sex (reference: male)1.887 (1.262).241.145Pre-Cold T2*.684 (.502).257.182Model 3Constant-3.046 (5.845).606.350.010*Age.073 (.073).183.325Sex (reference: male)2.224 (1.193).284.072Pre-Cold T2*.122 (.531).046.820% Body Fat.154 (.068).426.029*FF% Reduction and Liver Fat %As seen in Table 24, all models were found to be significantly associated with liver fat. In all cases, sex was not found to be a significant predictor of liver fat. In model 2, only FF% reduction was found to be a significant predictor of liver fat. Additionally, the inclusion of FF% reduction significantly increased the amount of variance predicted from 19.1% to 28.9%. In the full model, no variables were found to have a significant predictive value to liver fat. However, the addition of body fat percentage to the final model did slightly increase the amount of variance by 6.5%. Stepwise multiple regression analysis between liver fat, age, sex, FF% reduction and % body fat. Model C: FF% Reduction and Liver Fat %VariableUnstd β (SE)βp-valueModel SummaryR2p-valueModel 1Constant.336 (2.245).882.191.034*Age.160 (.065).398.020*Sex (reference: male)2.115 (1.268).270.105Model 2Constant3.542 (2.700).200.289.018*Age.102 (.069).257.149Sex (reference: male)2.279 (1.285).283.087FF% Reduction-.516 (.252)-.349.050*Model 3Constant.178 (3.295).957.354.013*Age.070 (.070).177.320Sex (reference: male)2.252 (1.247).280.082FF% Reduction-.233 (.297)-.158.439% Body Fat.127 (.076).347.104DISCUSSIONAs previously noted in Chapter 1, the increasing prevalence of NAFLD worldwide is worrisome as there are no effective pharmacological treatments for NAFLD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cld.2015.01.012", "ISBN" : "9780323393409", "ISSN" : "15578224", "PMID" : "25921668", "abstract" : "Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies.", "author" : [ { "dropping-particle" : "", "family" : "Noureddin", "given" : "Mazen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinella", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinics in Liver Disease", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "361-379", "publisher" : "Elsevier Inc", "title" : "Nonalcoholic Fatty Liver Disease, Diabetes, Obesity, and Hepatocellular Carcinoma", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁵", "plainTextFormattedCitation" : "45", "previouslyFormattedCitation" : "⁴⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }45. Recently, the role of BAT in NAFLD development has previously been investigated in both rodents ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/cr.2013.64", "ISSN" : "1001-0602", "PMID" : "23649313", "abstract" : "\\nSupplementary information available for this article at ", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Xiaomeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Zongji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Xiaoming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Minghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Lan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Yanyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chi", "given" : "Qingsheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Dehua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Zhaoyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Chenzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yiming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xue", "given" : "Yaoming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Wanzhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Research", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "851-854", "title" : "Brown adipose tissue transplantation improves whole-body energy metabolism", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/en.2014-1598", "ISSN" : "19457170", "PMID" : "25830704", "abstract" : "Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased \u03b23-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Xiaomeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Siping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Yilin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Minghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Zongji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Meng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Qianwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Chuanhai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yuan", "given" : "Xiaoxue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Lieqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Yuanyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Dehua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhan", "given" : "Jicheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Hyuek Jong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speakman", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Wanzhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrinology", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2461-2469", "title" : "Brown adipose tissue transplantation reverses obesity in Ob/Ob mice", "type" : "article-journal", "volume" : "156" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/nm.3766", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "25485911", "abstract" : "Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue, but its thermogenic potential is reduced with obesity and type 2 diabetes for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively. Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts \u03b2-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.", "author" : [ { "dropping-particle" : "", "family" : "Crane", "given" : "Justin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palanivel", "given" : "Rengasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottillo", "given" : "Emilio P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bujak", "given" : "Adam L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Huaqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ford", "given" : "Rebecca J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bl\u00fcmer", "given" : "Regje M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fullerton", "given" : "Morgan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yabut", "given" : "Julian M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Janice J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghia", "given" : "Jean-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamza", "given" : "Shereen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schertzer", "given" : "Jonathan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dyck", "given" : "Jason R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Waliul I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinberg", "given" : "Gregory R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2", "8" ] ] }, "page" : "166-172", "title" : "Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^60\u201362", "plainTextFormattedCitation" : "60\u201362", "previouslyFormattedCitation" : "^59\u201361" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }60–62 and adult humans ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59; in these studies, researchers showed that BAT had protective effects against NAFLD. However, studies in humans were limited in that they were retrospective in nature and restricted to a clinical sample ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. 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We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59. Thus, the primary objective of this chapter was to determine if associations between BAT and liver fat still existed in a tightly-controlled (i.e. extensive exclusion criteria) healthy population. In this study, liver fat was moderately correlated with both BAT characteristics (i.e. pre-cold FF% or pre-cold T2*) and BAT activity (i.e. FF% reduction). These findings were consistent with retrospective studies in adult humans that showed individuals with detectable BAT activity (as measured by 18F-FDG PET-CT) had lower NAFLD prevalence, decreased liver fat content (as measured by CT) and better hepatic function (i.e. lower liver enzymes levels) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2036.2011.04723.x", "ISSN" : "02692813", "PMID" : "21631560", "abstract" : "BACKGROUND The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.", "author" : [ { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purnak", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozguven", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurt", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atug", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary Pharmacology & Therapeutics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "318-323", "title" : "Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00259-015-3166-7", "ISBN" : "1619-7089 (Electronic) 1619-7070 (Linking)", "ISSN" : "16197089", "PMID" : "26283505", "abstract" : "PURPOSE The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.", "author" : [ { "dropping-particle" : "", "family" : "Ozguven", "given" : "Salih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ones", "given" : "Tunc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Yusuf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turoglu", "given" : "H. Turgut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imeryuz", "given" : "Nese", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Nuclear Medicine and Molecular Imaging", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2", "19" ] ] }, "page" : "355-361", "title" : "The role of active brown adipose tissue in human metabolism", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^58,59", "plainTextFormattedCitation" : "58,59", "previouslyFormattedCitation" : "^57,58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58,59. Findings reported in this thesis showed for the first time that BAT outcomes were closely associated with liver fat content in a healthy controlled population. In these individuals, a browner phenotype (i.e. lower values of pre-cold FF% or pre-cold T2*) or higher BAT activity (i.e. greater FF% reduction) were associated with lower liver fat content. Taken together, these findings suggest that BAT may have an important role in liver metabolism in adult humans. Although no human studies have directly investigated the role of BAT in liver lipid metabolism, findings in rodents have shown that BAT has a significant effect in shifting substrate clearance from the liver to BAT depots during BAT activation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.2297", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "21258337", "abstract" : "Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.", "author" : [ { "dropping-particle" : "", "family" : "Bartelt", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruns", "given" : "Oliver T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimer", "given" : "Rudolph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hohenberg", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ittrich", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peldschus", "given" : "Kersten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaul", "given" : "Michael G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tromsdorf", "given" : "Ulrich I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weller", "given" : "Horst", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waurisch", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eychm\u00fcller", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordts", "given" : "Philip L S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinninger", "given" : "Franz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruegelmann", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freund", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkel", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heeren", "given" : "Joerg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "200-205", "publisher" : "Nature Publishing Group", "title" : "Brown adipose tissue activity controls triglyceride clearance", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/en.2015-1092", "ISSN" : "19457170", "PMID" : "26372178", "abstract" : "High glucocorticoid concentrations are accompanied by metabolic side effects such as high plasma triglyceride (TG) concentrations. Liver, brown adipose tissue (BAT) and white adipose tissue are important regulators of plasma TG. Exposure to 4\u00b0C reduces plasma TG concentrations, and we therefore aimed to study the interaction between glucocorticoid excess and 24 hours of exposure to 4\u00b0C on lipid metabolism. For this, mice were implanted with 50-mg corticosterone or control pellets and housed for 24 hours at 23\u00b0C or 4\u00b0C 1 week later, after which various aspects of TG metabolism in liver, BAT, and white adipose tissue were studied. Corticosterone treatment resulted in a 3.8-fold increase of plasma TG concentrations. Increased TG was normalized by cold exposure, an effect still present 24 hours after cold exposure. Corticosterone treatment increased hepatic TG content by 3.5-fold and provoked secretion of large, TG-rich very low density lipoprotein particles. Cold exposure reduced very low density lipoprotein-TG secretion by approximately 50%. Corticosterone strongly decreased BAT activity: BAT weight increased by 3.5-fold, whereas uncoupling protein 1 (Ucp1) mRNA expression and Ucp1 protein content of BAT were reduced by 75% and 60%, respectively. Cold exposure partially normalized these parameters of BAT activity. The uptake of TG by BAT was not affected by corticosterone treatment but was increased 4.5-fold upon cold exposure. In conclusion, cold exposure normalizes corticosterone-induced hypertriglyceridemia, at least partly via activating BAT.", "author" : [ { "dropping-particle" : "", "family" : "Beukel", "given" : "Johanna C.", "non-dropping-particle" : "Van Den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boon", "given" : "Mariette R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steenbergen", "given" : "Jacobie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rensen", "given" : "Patrick C.N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meijer", "given" : "Onno C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Themmen", "given" : "Axel P.N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grefhorst", "given" : "Aldo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrinology", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "4115-4128", "title" : "Cold exposure partially corrects disturbances in lipid metabolism in a male mouse model of glucocorticoid excess", "type" : "article-journal", "volume" : "156" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^63,64", "plainTextFormattedCitation" : "63,64", "previouslyFormattedCitation" : "^62,63" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63,64. For example, Bartelt et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.2297", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "21258337", "abstract" : "Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.", "author" : [ { "dropping-particle" : "", "family" : "Bartelt", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruns", "given" : "Oliver T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimer", "given" : "Rudolph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hohenberg", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ittrich", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peldschus", "given" : "Kersten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaul", "given" : "Michael G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tromsdorf", "given" : "Ulrich I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weller", "given" : "Horst", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waurisch", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eychm\u00fcller", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordts", "given" : "Philip L S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinninger", "given" : "Franz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruegelmann", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freund", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkel", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heeren", "given" : "Joerg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "200-205", "publisher" : "Nature Publishing Group", "title" : "Brown adipose tissue activity controls triglyceride clearance", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶³", "plainTextFormattedCitation" : "63", "previouslyFormattedCitation" : "⁶²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63 reported that cold-induced BAT thermogenesis in rodents resulted in increased BAT TG uptake, which subsequently reduced triglyceride-rich lipoprotein uptake into the liver. In another study, BAT activation was shown to lower VLDL production from the liver and liver de novo lipogenesis in rodents with hyperlipidemia ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/en.2015-1092", "ISSN" : "19457170", "PMID" : "26372178", "abstract" : "High glucocorticoid concentrations are accompanied by metabolic side effects such as high plasma triglyceride (TG) concentrations. Liver, brown adipose tissue (BAT) and white adipose tissue are important regulators of plasma TG. Exposure to 4\u00b0C reduces plasma TG concentrations, and we therefore aimed to study the interaction between glucocorticoid excess and 24 hours of exposure to 4\u00b0C on lipid metabolism. For this, mice were implanted with 50-mg corticosterone or control pellets and housed for 24 hours at 23\u00b0C or 4\u00b0C 1 week later, after which various aspects of TG metabolism in liver, BAT, and white adipose tissue were studied. Corticosterone treatment resulted in a 3.8-fold increase of plasma TG concentrations. Increased TG was normalized by cold exposure, an effect still present 24 hours after cold exposure. Corticosterone treatment increased hepatic TG content by 3.5-fold and provoked secretion of large, TG-rich very low density lipoprotein particles. Cold exposure reduced very low density lipoprotein-TG secretion by approximately 50%. Corticosterone strongly decreased BAT activity: BAT weight increased by 3.5-fold, whereas uncoupling protein 1 (Ucp1) mRNA expression and Ucp1 protein content of BAT were reduced by 75% and 60%, respectively. Cold exposure partially normalized these parameters of BAT activity. The uptake of TG by BAT was not affected by corticosterone treatment but was increased 4.5-fold upon cold exposure. 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Based on these findings, the mechanistic relationship between BAT and liver fat in adult humans is currently not known and therefore future research that aims to examine the potential mechanism on the interplay between BAT and liver is warranted.As noted in Section 5.4.3, a stepwise multiple regression analyses was conducted to better understand how each covariate was independently related to liver fat content. Age and sex were first added to the model which was followed by a BAT MR outcome (i.e. pre-cold FF%, pre-cold T2* or FF% reduction) and then body fat percentage. This specific order was chosen to evaluate the effects of each BAT MR outcome on liver fat while first accounting for biological differences between participants. With only age and sex in the model, pre-cold FF% and FF% reduction were found to significantly predict liver fat while pre-cold T2* was not found to be a significant predictor of liver fat. Additionally, the inclusion of each BAT MR outcome resulted in a significant and considerable increase in variance in all regression models. Interestingly, the independent relationship between pre-cold FF% and FF% reduction with hepatic fat disappeared with the addition of body fat percentage. Taken together, these results suggest that the relationship of BAT with hepatic fat is not independent of body fat percentage. That is, the indirect relationship between BAT and liver fat may be explained by the effects of BAT on adiposity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0022-3514.51.6.1173", "ISBN" : "0022-3514\\r1939-1315", "ISSN" : "1939-1315", "PMID" : "3806354", "abstract" : "Baron, R. M., & Kenny, D. A. (1986). The moderator\u2013mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. 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However, it will be difficult to differentiate the relative influence of body fat and hepatic fat as they are tightly related. These results extend the findings reported in rodent studies that showed BAT has a protective effect against NAFLD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/cr.2013.64", "ISSN" : "1001-0602", "PMID" : "23649313", "abstract" : "\\nSupplementary information available for this article at ", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Xiaomeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Zongji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Xiaoming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Minghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Lan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Yanyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chi", "given" : "Qingsheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Dehua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Zhaoyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Chenzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yiming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xue", "given" : "Yaoming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Wanzhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Research", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "851-854", "title" : "Brown adipose tissue transplantation improves whole-body energy metabolism", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/en.2014-1598", "ISSN" : "19457170", "PMID" : "25830704", "abstract" : "Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased \u03b23-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Xiaomeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Siping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Yilin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Minghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Zongji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Meng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Qianwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Chuanhai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yuan", "given" : "Xiaoxue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Lieqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Yuanyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Dehua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhan", "given" : "Jicheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Hyuek Jong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speakman", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Wanzhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrinology", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2461-2469", "title" : "Brown adipose tissue transplantation reverses obesity in Ob/Ob mice", "type" : "article-journal", "volume" : "156" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/nm.3766", "ISBN" : "1546-170X (Electronic)\\r1078-8956 (Linking)", "ISSN" : "1078-8956", "PMID" : "25485911", "abstract" : "Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue, but its thermogenic potential is reduced with obesity and type 2 diabetes for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively. Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts \u03b2-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.", "author" : [ { "dropping-particle" : "", "family" : "Crane", "given" : "Justin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palanivel", "given" : "Rengasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mottillo", "given" : "Emilio P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bujak", "given" : "Adam L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Huaqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ford", "given" : "Rebecca J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bl\u00fcmer", "given" : "Regje M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fullerton", "given" : "Morgan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yabut", "given" : "Julian M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Janice J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghia", "given" : "Jean-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamza", "given" : "Shereen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schertzer", "given" : "Jonathan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dyck", "given" : "Jason R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Waliul I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinberg", "given" : "Gregory R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2", "8" ] ] }, "page" : "166-172", "title" : "Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^60\u201362", "plainTextFormattedCitation" : "60\u201362", "previouslyFormattedCitation" : "^59\u201361" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }60–62. It is important to note that in these rodent studies, treatments were employed with the intention of increasing BAT volume or activity, which may explain the direct relationship between BAT and NAFLD in these studies. In this study, a one-time acute cold exposure protocol was used to stimulate BAT activity, which may not be enough to elicit changes in whole-body energy metabolism. This could potentially explain the indirect relationship found in this study between BAT outcomes and liver fat after accounting for body fat percentage. Taken together, findings in this thesis provide strong supporting data that BAT has an important role in controlling liver lipid content, however, the extent of this role remains to be seen. CONCLUSIONSUMMARY OF FINDINGSThe first section of this thesis highlighted the steps undertaken in the development and design of an MRI protocol to measure BAT. In this study, a highly reliable MRI segmentation protocol was developed that is capable of measuring BAT characteristics and activity. The high inter-rater reliability reported in this project was attributed to the use of semi-automated segmentation techniques typically associated with less rater subjectivity and operator bias. In this study, the use of the broad FF range (30 to 100%) was found to be more sensitive in characterizing BAT activity than the narrow range (50 to 80%) since changes in the lower and higher FF range were not being captured in the narrower FF range. Additionally, the inclusion of T2* mask in the segmentation process resulted in a significant decline in the number of voxels in FF ranges consistent with white adipose tissue (WAT), suggesting the successful exclusion of WAT in this region. The second part of this project evaluated the effectiveness of the newly developed MRI protocol in detecting BAT. Based on findings in this project, differences in MR signatures were not found to exist between SCV BAT and posterior neck SAT, suggesting that BAT may still be present in this region, although it is either inactive or weakly activated. In comparison, FF% values in abdominal SAT were significantly higher when compared to SCV BAT, where abdominal SAT showed FF% distributions that were more representative of WAT. The cold exposure protocol used in this study was found to be more effective in eliciting changes in BAT MR outcomes when compared to the literature, as shown by the greater decrease in FF% and T2* values after cooling. Additionally, the newly developed segmentation protocol was sensitive in detecting changes in FF% after cold exposure, suggesting that this segmentation protocol is capable of differentiating individuals with varying BAT activity. Finally, findings in this study provide supporting data that MRI could be used to detect BAT activity independent of cold exposure, as shown by the strong association between pre-cold FF% and BAT activity (i.e. FF% reduction) in the SCV area. The second objective examined the relationship between BAT MR outcomes and known covariates of BAT. In this study, BAT characteristics (i.e. pre-cold FF% or pre-cold T2*) and BAT activity (i.e. FF% reduction) were associated with age and body fat percentage, consistent with previous reports in the literature. T2* reduction was not. MR measures of BAT were related to age and body fat percentage as predicted based on methods that utilized 18F-FDG PET-CT to measure BAT activity. No associations were found between BAT MR outcomes and sex or outdoor temperature. The lack of association between these variables were attributed to the strengths of the study methodology that included the use of an acclimatization period prior to BAT measurements and consistent delivery of cold exposure as well as the minimization of hormone fluctuation in female individuals by timing studies to the participant’s menstrual cycle. Finally, with the use of multivariate modelling, body fat percentage was found to play a larger role than sex or age in defining BAT MR outcomes. The final objective of this thesis was to assess the relationship between BAT and liver fat accumulation before and after adjusting for potential covariates. Findings in this study showed for the first time that BAT outcomes were closely associated with liver fat in a healthy population; however, the potential mechanism underlying this relationship is currently not known. Additionally, in multivariate modelling, the relationship between BAT outcomes and liver fat content is potentially mediated by body fat percentage. Taken together, findings in this thesis provide strong supporting data that BAT has an important role in regulating liver lipid content, however, the extent and mechanisms remain to be elucidated.LIMITATIONS The segmentation protocol was limited in that post-cold images were not aligned or registered to pre-cold images which could have introduced more variability to the segmentation process. The software’s registration tool was originally designed for brain imaging. Brain images are far more consistent than images acquired in the SCV region. This may explain the software’s inability to register images in the SCV region. Additionally, BAT MR outcomes were not validated to 18F-FDG PET-CT, the current gold standard in measuring BAT volume and activity. Validation of BAT outcomes (as measured by MRI) were not conducted in this study due to the lack of a dedicated research PET-CT scanner. Given that recruitment for the study is still ongoing, data presented in this thesis are incomplete and should be considered as preliminary analyses. Thus, the study was limited in its current sample size and the distribution of participant characteristics were often skewed including variables such as age, sex and BMI. The narrow size of the scanner was also a limiting factor since this meant excluding eligible participants with more severe obesity. FUTURE DIRECTIONSSince the target sample size (n = 60) has not been reached at the time this thesis was written, one of the main directions moving forward is to complete recruitment for the study. Additionally, analyses presented in thesis should be re-evaluated to determine if the preliminary findings and interpretations presented in this project still holds true with the addition of more participants. As discussed previously in this thesis, the research group was able to develop a highly reliable MRI protocol capable of detecting BAT characteristics and activity. However, this protocol was not tested for reproducibility and repeatability. Given the importance of these measures in demonstrating the use of MRI as a standardized imaging modality for the detection of BAT, future studies are warranted to determine if this specific protocol is reproducible and repeatable. Given that the use of MR techniques such as FF% and T2* provide distinct information about BAT, combining these two measures might better reflect BAT characteristics or activity. However, the use of water-fat MRI including FF% and T2* is limited by its spatial resolution (i.e. signals are not specific to BAT due to partial volume effects). Thus, other MRI techniques such as intermolecular zero-quantum coherence (iZQC), an MR technique capable of differentiating BAT and WAT at an adipocyte level should be explored. In the current study, the effects of cold exposure on WAT MR signatures specifically FF% and T2* was only evaluated for posterior neck SAT. However, findings in this study suggest that this region may not be a suitable WAT depot as this region may contain weakly activated BAT. Therefore, a crucial next step is to assess the effects of cold exposure in fat depots void of BAT such as abdominal SAT. Lastly, preliminary analyses showed that BAT may have an important role in regulating liver content in adult humans. That is a higher BAT activity was associated with lower liver fat. However, the mechanistic relationship between BAT and liver fat is currently not known and therefore future studies that aim to examine the interplay between BAT and liver is warranted. APPENDIXSUPPLEMENTARY FIGURES AND TABLES (METHODS)List of VariablesComplete list of VariablesCategoryVariable Name (units)Variable TypeObjective#1#2#3AnthropometricsAge (yrs)Continuous???Sex (male or female)Categorical???Weight (kg)Continuous???Height (cm)Continuous???BMI (kg/m2)Continuous???Waist Circumference (cm)Continuous???Body CompositionBody Fat Percentage (%)Continuous???Fat Mass (kg)Continuous???Lean Mass (kg)Continuous???Outdoor Temperature1 hour prior to visit 2 (°C)Continuous?24 hours prior to visit 2 (°C)Continuous?7 days prior to visit 2 (°C)Continuous?SCV BAT MR OutcomesPre-Cold SCV BAT FF (%)Continuous???Post-Cold SCV BAT FF (%)Continuous???Pre-Cold SCV BAT T2* (ms)Continuous???Post-Cold SCV BAT T2* (ms)Continuous???SCV BAT FF Reduction (%)Continuous???SCV BAT T2* Reduction (ms)Continuous??Pre-Cold SCV Volume (cm3)Continuous?Post-Cold SCV Volume (cm3)Continuous?Posterior Neck SAT MR OutcomesPre-Cold Posterior Neck SAT FF (%)Continuous?Post-Cold Posterior Neck SAT FF (%)Continuous?Pre-Cold Posterior Neck SAT T2* (ms)Continuous?Post-Cold Posterior Neck SAT T2* (ms)Continuous?Posterior Neck WAT FF Reduction (%)Continuous?Posterior Neck WAT T2* Reduction (ms)Continuous?Abdominal SAT MR OutcomesAbdominal SAT FF (%)Continuous?Abdominal SAT T2* (ms)Continuous?Liver Fat Liver Fat (%)Continuous?MRI Literature Tables Summarized FF% ranges from the 12 articles that used FF% to measure BAT. * Unless otherwise stated, the segmentation location for BAT was the entire SCV region. FF% ranges were only reported for children and adults. PAPERSPOPULATIONBAT RANGE (LOCATION)WAT RANGE (LOCATION)Holstila et al. (2017) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁶", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66Adults73.0 to 87.0 Threshold: 50-100%83.0 to 94.0Koskensalo et al. (2017) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2016-3086", "ISSN" : "19457197", "PMID" : "28323929", "abstract" : "Background and aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron-emission-tomography (PET). The aim of this study was to use proton Magnetic Resonance Spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of brown and white adipose tissue (WAT) are associated with BAT metabolic activity determined by 18F-FDG-PET. Materials and methods Ten healthy subjects (4f/6m, 25-45 y) were studied using PET-MRI during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on 8 subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid burning capacity of BAT associated with whole-body insulin sensitivity. In cold exposure the FF of BAT was lower than at room temperature, and further, cold-induced FF of BAT associated inversely with HDL and directly with LDL cholesterol. Conclusion 1H MRS derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid burning capacity of BAT and whole-body insulin sensitivity emphasises the role of BAT in glucose handling. Furthermore, the relation of FF to HDL and LDL suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.", "author" : [ { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Virva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskola", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saunavaara", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1200-1207", "title" : "Human brown adipose tissue temperature and fat fraction are related to its metabolic activity", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁷", "plainTextFormattedCitation" : "67", "previouslyFormattedCitation" : "⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }67Adults73.0 to 83.6 (left SCV via 1H-MRS)* 1 voxel = 1.75mm x 2mm x 1.5mm81.7 to 90.4(upper posterior thoracic)Franssens et al. (2016) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.25594", "ISSN" : "15222586", "PMID" : "28130811", "abstract" : "PURPOSE To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "497-504", "title" : "Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁸", "plainTextFormattedCitation" : "68", "previouslyFormattedCitation" : "⁶⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }68Adults68.0 to 87.076.0 to 93.0(posterior to trapezius)McCallister et al. (2016) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁹", "plainTextFormattedCitation" : "69", "previouslyFormattedCitation" : "⁶⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }69Adults56.0 to 87.0Threshold: 40 to 100%NOT ANALYZEDStahl et al. (2016) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.25364", "ISSN" : "15222586", "PMID" : "27421080", "abstract" : "PURPOSE To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI). MATERIALS AND METHODS The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23\u00b0C, 20 min), cooling (12\u00b0C, 90 min), and a final warming phase (37\u00b0C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue. RESULTS Temperature measurements showed a decrease of 3.8 \u00b1 1.0\u00b0C of the back skin temperature, while the body temperature stayed constant at 37.2 \u00b1 0.9\u00b0C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 \u00b1 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 \u00b1 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]). CONCLUSION We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling. J. Magn. Reson. Imaging 2016.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Vanessa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freitag", "given" : "Martin T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Floca", "given" : "Ralf O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Moritz C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umathum", "given" : "Reiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berriel Diaz", "given" : "Mauricio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzig", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Marc Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitrakopoulou-Strauss", "given" : "Antonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rink", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladd", "given" : "Mark E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Armin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369-380", "title" : "In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁰", "plainTextFormattedCitation" : "70", "previouslyFormattedCitation" : "⁶⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }70Adults56.0 to 74.0(small ROI at left and right interscapular)* Mean ROI (SD) = 1.31 mL (1.43 mL)Pre-Cold: 60 to 80%Post-Cold: ≥ 30%73.0 to 78.0(posterior to trapezius)Gifford et al. (2016) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷¹", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "⁷⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71Adults47.0 to 79.0Threshold: 50 to 100%90.5 to 95.5(umbilicus level)Franssens et al. (2015) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/nbm.3444", "ISBN" : "1099-1492 (Electronic)\\r0952-3480 (Linking)", "ISSN" : "10991492", "PMID" : "26620447", "abstract" : "The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright (c) 2015 John Wiley & Sons, Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Franssens", "given" : "Bas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eikendal", "given" : "Anouk L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leiner", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visseren", "given" : "Frank L.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogduin", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NMR in Biomedicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "48-56", "title" : "Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷²", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "⁷¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72Adults78.6 to 84.087.2 to 91.5(posterior to trapezius)Franz et al. (2015) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2967/jnumed.115.160770", "ISSN" : "0161-5505", "PMID" : "26272809", "abstract" : "UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET.\\n\\nMETHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis.\\n\\nRESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT.\\n\\nCONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.", "author" : [ { "dropping-particle" : "", "family" : "Franz", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karampinos", "given" : "D. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rummeny", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souvatzoglou", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beer", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nekolla", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwaiger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiber", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Nuclear Medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1742-1747", "title" : "Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷³", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "⁷²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73Children and Elderly AdultsChildren: 32.0 to 94.0Elderly: 84.0 to 94.0Children: 81.0 to 97.0Elderly: 86.0 to 97.0(gluteal)Deng et al. (2015) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁴", "plainTextFormattedCitation" : "74", "previouslyFormattedCitation" : "⁷³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74Children72.0 to 93.0NOT ANALYZEDLundstr?m et al. (2015) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁴", "plainTextFormattedCitation" : "44", "previouslyFormattedCitation" : "⁷⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }44Adults66.3 to 88.7Threshold: ≥ 40%77.0 to 91.8(posterior to trapezius)Hu et al. (2012) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38Children44.5 to 89.970.7 to 94.2(adjacent to SCV)Hu et al. (2012) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37Adults52.0 to 93.982.8 to 95.4(adjacent to SCV)Summarized T2* or R2* ranges from the 7 articles that used either T2* or R2* to measure BAT. * Unless otherwise stated, the segmentation location for BAT was the entire SCV region. T2* or R2* ranges were only reported for children and adults. PAPERSPOPULATIONBAT WAT Holstila et al. (2017) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2017.02.001", "ISSN" : "15328600", "PMID" : "28403942", "abstract" : "Objective Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water\u2013fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. Material and methods The supraclavicular area of 13 volunteers was studied on 3 T PET\u2013MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. Results The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18F-FDG PET. Conclusions Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.", "author" : [ { "dropping-particle" : "", "family" : "Holstila", "given" : "Milja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pesola", "given" : "Marko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saari", "given" : "Teemu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskensalo", "given" : "Kalle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raiko", "given" : "Juho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borra", "given" : "Ronald J.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuutila", "given" : "Pirjo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkkola", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Virtanen", "given" : "Kirsi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: Clinical and Experimental", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "23-30", "publisher" : "Elsevier Inc.", "title" : "MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁶", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66AdultsT2*: 12.0 to 19.5 msT2*: 18.0 to 25.0 ms(no location provided)McCallister et al. (2017) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/mrm.26589", "ISSN" : "15222594", "PMID" : "28112821", "abstract" : "Purpose: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. Methods: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. Results: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. Conclusion: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med, 2017. \u00a9 2017 International Society for Magnetic Resonance in Medicine.", "author" : [ { "dropping-particle" : "", "family" : "McCallister", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burant", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Branca", "given" : "Rosa Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Magnetic Resonance in Medicine", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1922-1932", "title" : "A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁹", "plainTextFormattedCitation" : "69", "previouslyFormattedCitation" : "⁶⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }69AdultsR2*: 52 to 118 s-1NOT ANALYZEDGifford et al. (2016) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpendo.00482.2015", "ISBN" : "01931849", "ISSN" : "0193-1849", "PMID" : "27166284", "abstract" : "Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means \u00b1 SD; 60.2 \u00b1 7.6 vs. 62.4 \u00b1 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 \u00b1 11.5 vs. -74.5 \u00b1 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.", "author" : [ { "dropping-particle" : "", "family" : "Gifford", "given" : "Aliya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towse", "given" : "Theodore F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Ronald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avison", "given" : "Malcolm J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "E. Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Endocrinology And Metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "95-104", "title" : "Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷¹", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "⁷⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71AdultsR2*: 70 to 179 s-1Threshold: R2* < 150 s-1R2*: 40 to 65 s-1(umbilicus level)Deng et al. (2015) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00247-015-3391-z", "ISSN" : "14321998", "PMID" : "26092667", "abstract" : "Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children.\\r\\nTo exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status.\\r\\nTwenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status.\\r\\nMRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028).\\r\\nThis study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.", "author" : [ { "dropping-particle" : "", "family" : "Deng", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoeneman", "given" : "Samantha E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huiyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon", "given" : "Soyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rigsby", "given" : "Cynthia K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Josefson", "given" : "Jami L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Radiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1682-1689", "title" : "MRI characterization of brown adipose tissue in obese and normal-weight children", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁴", "plainTextFormattedCitation" : "74", "previouslyFormattedCitation" : "⁷³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74ChildrenT2*: 8.7 to 15.6 ms NOT ANALYZEDLundstr?m et al. (2015) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0126705", "ISSN" : "19326203", "PMID" : "25928226", "abstract" : "OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.\\n\\nMATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).\\n\\nRESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).\\n\\nCONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strand", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergsten", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahlstr\u00f6m", "given" : "H\u00e5kan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kullberg", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Romanovsky", "given" : "Andrej A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "30" ] ] }, "page" : "1-13", "title" : "Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁴", "plainTextFormattedCitation" : "44", "previouslyFormattedCitation" : "⁷⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }44AdultsR2*: 19.1 to 26.3 s-1R2*: 15.7 to 25.0 s-1Hu et al. (2012) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jmri.24053", "ISBN" : "1522-2586 (Electronic) 1053-1807 (Linking)", "ISSN" : "10531807", "PMID" : "23440739", "abstract" : "PURPOSE To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggabao", "given" : "Patricia C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Magnetic Resonance Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "885-896", "title" : "Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38ChildrenT2*: 11.9 to 25.5T2*: 15.0 to 44.4(adjacent to SCV)Hu et al. (2012) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.12.8996", "ISBN" : "2122633255", "ISSN" : "0361803X", "PMID" : "23255760", "abstract" : "OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Houchun H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkins", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Jonathan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilsanz", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "177-183", "title" : "Characterization of human brown adipose tissue by chemical-shift water-fat MRI", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37AdultsT2*: 12.5 to 33.4T2*: 28.8 to 40.1(adjacent to SCV)Exclusion Criteria List of excluded medicationsClass of DrugsListDrugs affecting β-adrenergic receptorβ blockersAcebutolol (Sectral)Atenolol (Tenormin)Bisoprolol (Zebeta)Metoprolol (Lopressor, Toprol-XL)Nadolol (Corgard)Propranolol (Inderal LA, InnoPran XL) Asthma/COPD beta-adrenergic agonistsBambuterol (Bambec, Oxeol)Bitolterol mesylate (Tornalate)Clenbuterol (Dilaterol, Spiropent, Ventipulmin)Fenoterol (Berotec N)Formoterol (Foradil, Zenhale, Symbicort, Forpack Discair, Oxeze/Oxis)Isoprenaline/ Isoproterenol (Isuprel)Levosalbutamol (Levalbuterol, Xopenex)Metaproterenol (Alupent)Olodaterol (Striverdi)Pirbuterol (Maxair)ProcaterolSalbutamol (Albuterol, Ventolin)Salmeterol (Serevent Diskus)Terbutaline (Bricanyl)Vilanterol (Breo Ellipta, Relvar Ellipta)Others Mirabegron (Myrbetriq)Drugs associated with hepatic steatosis CorticosteroidsBetamethasone (Celestone)Budesonide (Pulmicort, Entocort EC)Cortone Acetate (Cortone)CotoloneDexamethasone (Decadron)Fludrocortisone (Florinef Acetate)Methylprednisolone (Medrol, Methylpred-DP)Prednisone (Bubbli-Pred, Deltasone, Prednicot, Prelone, Pediapred 5, Pms-prednisolone)Triamcinolone (Aristocort)TetracyclineDemeclocycline (Declomycin)Doxycycline (Doryx, Vibramycin)Minocycline (Dynacin, Minocin, Monodox)Oxytetracycline (Terramycin)Tetracycline (Achromycin)Tigecycline (Tygacil) OtherAmiodarone (Cordarone, Nexterone, Pacerone)L-asparaginase (Elspar)Methotrexate (Rheumatrex, Trexall)Tamoxifen(Nolvadex)Valproic acid (Depakote, Depakote ER, Depakote Sprinkle, Depakene, Depacon, Stavzor)Anti-hyperglycemic drugsAlpha-Glucosidase InhibitorAcarbose (Precose)Miglitol (Glyset)BiguanidesMetformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet)Metformin combination drugsActoplus Met AvandametDuetactGlucovanceJanumetJentadueto KomboglyzeMetaglip PrandiMetDipeptidyl peptidase-4 (DPP-4) inhibitorAlogliptin (Nesina) Canagliflozin (Invokana)Dapagliflozin (Farxiga)Linagliptin (Tradjenta) Saxagliptin (Onglyza) Sitagliptin (Januvia)Glucagon-like peptideExenatide (Exendin-4, Byetta)Liraglutide (Victoza)Lixisenatide (Lyxumia)MeglitinidesRepaglinide (GlucoNorm, Prandin, NovoNorm)Nateglinide (Starlix) InsulinSulfonylureaChlorpropamide (Diabinese)Glimepiride (Amaryl)Glipizide (Glucotrol, Glucotrol XL)Glyburide (DiaBeta, Glynase PresTab, Micronase)TolbutamideYolazamide ThiazolidinedionesPioglitazone (Actos)Rosiglitazone (Avandia)HIV drugsHAARTAntidepressants, anxiolytic drugs, anti-psychotic drugs5-HT2 Receptor AntagonistsTrazodone (Desyrel, Oleptro, Trazorel, Trialodine, Trittico)5-HT3 Receptor AntagonistsVortioxetine (Brintellix, Trintellix)Dopamine Reuptake BlockerBupropion (Wellbutrin)MAOIs (Monoamine oxidase inhibitors)Isocarboxazid (Marplan)Phenelzine (Nardil)Selegiline (Emsam)Tranylcypromine (Parnate)SNRIs (Serotonin and norepinephrine reuptake inhibitors)Desvenlafaxine (Pristiq)Duloxetine (Cymbalta)Venlafaxine (Effexor XR)SSRIs (Selective serotonin reuptake inhibitor)Citalopram (Celexa)Escitalopram (Lexapro)Fuoxetine (Prozac)Fuvoxamine (Luvox)Paroxetine (Paxil)Sertraline (Zoloft)Tetracyclic AntidepressantMaprotiline (Teva-Maprotiline)Mirtazapine (Tera-Mirtazapine)Tricyclic medicationAmitriptyline (Elavil)Amoxapine (Asendin)Clomipramine (Anafranil)Desipramine (Norpramin)Doxepin (Silenor)Imipramine (Tofranil)Nortriptyline (Pamelor)Protriptyline (Vivactil)Trimipramine (Surmontil)Thyroid drugsAnti-thyroidMethimazole (Tapazole)Propylthiouracil (Propyl-Thyracil or PTU)Thyroidlevothyroxine (T4) (Levothroid, Levoxyl, Synthroid, Tirosint, Unithroid)liothyronine (T3) (Cytomel)liotrix (T3 and T4) (Thyrolar)Antiemetic (5HT3 antagonists)Dolasetron (Anzemet)Granisetron (Granisetron Hydrochloride)Ondansetron (Zofran)Palonosetron (Aloxi)Drugs associated with serotonin metabolismAmphetamineDextromethorphanMetoclopramideList of excluded conditionsConditionsListDiseases associated with brown adipose tissue dysfunctionAdrenal gland disorder (i.e. pheochromocytoma)HibernomaDiseases associated with hepatic steatosis and liver disordersAbetalipoproteinemia Celiac disease Cystic fibrosisGalactosemiaGlycogen storage diseaseHemochromatosisHepatitis B or CHepatocellular carcinoma (HCC)HomocystinuriaInflammatory bowel diseaseLipodystrophyPolycystic liver diseaseTyrosinemiaWeber-Christian syndromeWilson’s diseaseMR ParametersMRI protocol parameters for IDEAL-IQ Pulse Sequence: IDEAL-IQParameterSCVLiverAbdomenPatient EntryHead FirstFeet FirstPatient PositionSupineCoilHNS Head/Neck/ChestNeoCoil 32 Channel Torso ArrayOrientationAxialFlip angle43TEMin FullNumber of echoes6Echo Train Length 3Number of shots2Bandwidth 111.11Frequency axisBottom/UpPhase axisRight/LeftSpatial resolution (mm)1.48 x 1.481.33 x 1.331.56 x 1.56Acquired slice thickness (mm)485Imaging OptionsEDR, Fast, IDEAL, ARCMRI protocol parameters for LAVA-FLEXPulse Sequence: LAVA-FLEXParameterSCVLiverAbdomenPatient EntryHead FirstFeet FirstPatient PositionSupineCoilHNS Head/Neck/ChestNeoCoil 32 Channel Torso ArrayOrientationAxialFlip angle3TEMin FullTE22.22.62.5Number of echoes2TR3.74.34.1TI125Bandwidth 166.67Frequency axisBottom/UpPhase axisRight/LeftSpatial resolution (mm)1.48 x 1.481.33 x 1.331.56 x 1.56Acquired slice thickness (mm)485Imaging OptionsNPW, EDR, Fast, ARCEDR, Fast, ARCMRI Segmentation ProtocolAbdominal SATThe final segmentation protocol used to measure abdominal SAT is outlined below, in chronological order:1. Application of fat mask: to isolate adipose from non-adipose tissues and to exclude background noise2. FF Threshold Application (30 to 100%): to ensure that only voxels within that threshold range were included in the segmentation process3. Delineating ROI in Abdominal SAT: single-slice segmentation at L4-L5 disc; this specific disc was previously shown to accurately estimate total abdominal SAT volume ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "00029165", "PMID" : "17284730", "abstract" : "A single axial image measured between the 4th and 5th lumbar vertebrae (L4-L5) is most frequently chosen to approximate total abdominal visceral adipose tissue (VAT) volume, but growing evidence suggests that this measurement site is not ideal.", "author" : [ { "dropping-particle" : "", "family" : "Demerath", "given" : "Ellen W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Miryoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choh", "given" : "Audrey C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czerwinski", "given" : "Stefan A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siervogel", "given" : "Roger M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towne", "given" : "Bradford", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Clinical Nutrition", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "362-368", "title" : "Approximation of total visceral adipose tissue with a single magnetic resonance image", "type" : "article-journal", "volume" : "85" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/jid.2014.371", "ISBN" : "1046-7890", "ISSN" : "10467890", "PMID" : "24597427", "abstract" : "In a previous article,1 l attempted to assess the likely Impact of the most prominent versions of the therapeutic misconception (TM) on research subjects' informed consent. I concluded that the TM is not nearly as significant a concern as is commonly thought, and that focusing on it is more likely to undermine than promote research subjects' informed consent. A recent commentary rejects these conclusions, as least as they pertain to the \"consensus\" definition of the TM.2 The authors of the commentary argue that work on the TM remains central to ensuring the appropriateness of research subjects' consent and, by implication, the ethical acceptability of clinical research. The present work evaluates the arguments offered in support of these claims. This analysis reveals that the authors offer few substantive responses to my arguments, and the responses they do offer fail to undermine my prior conclusions. Furthermore, consideration of an additional issue-the emergence of learning healthcare systems-suggests that the TM is likely to be even less significant in the future, hence, focusing on it may be even more problematic than I argued previously. \u00a92013 by The Journal of Clinical Ethics. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Wendler", "given" : "David S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Ethics", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "387-394", "title" : "Problems with the consensus definition of the therapeutic misconception", "type" : "article-journal", "volume" : "24" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "^87,88", "plainTextFormattedCitation" : "87,88", "previouslyFormattedCitation" : "^87,88" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }87,884. Manually adding or removing regions: to ensure that only abdominal SAT was included in the segmentation process 5. Erosion of ROI (2D 3x3; jack structural element): to correct for any inherent partial volume effects present in the images Posterior Neck SATThe final segmentation protocol used to measure posterior neck SAT is outlined below, in chronological order: 1. Application of fat mask: to isolate adipose from non-adipose tissues and to exclude background noise2. FF Threshold Application (30 to 100%): to ensure that only voxels within that threshold range were included in the segmentation process3. Delineating ROI in Posterior Neck SAT: multi-slice segmentation along the C5-C6, C6-C7 and C7-T1 discs4. Erosion of ROI (2D 1x3; jack structural element): to correct for any inherent partial volume effects present in the imagesSUPPLEMENTARY FIGURES AND TABLES (RESULTS)Comparison of FF% DistributionSCV FF% distribution in a participant with high BAT activity (FF% reduction = 9.60%).SCV FF% distribution in a participant with low BAT activity (FF% reduction = 0.66%). SCV FF% distribution in a participant with a normal BMI (BMI = 24.4).SCV FF% distribution in a participant with an obese BMI (BMI = 31.7).Posterior Neck FF% distribution in a participant with a normal BMIPosterior Neck FF% distribution in a participant with an obese BMI Abdominal SAT FF% distribution in a participant with a normal BMI (BMI = 24.4). Abdominal SAT FF% distribution in a participant with an obese BMI (BMI = 31.7).SCV FF% distribution using only FF% mask and FF% + T2* mask in a participant with a normal BMI (BMI = 24.4). SCV FF% distribution using only FF% mask and FF% + T2* mask in a participant with an obese BMI (BMI = 31.7). SCV FF% distribution using only FF% mask and FF% + T2* mask in a participant with a high BAT activity (FF% reduction = 9.60%)SCV FF% distribution using only FF% mask and FF% + T2* mask in a participant with a low BAT activity (FF% reduction = 0.66%) Inter-Rater Reliability Reliability of SCV BAT FF% between three raters before and after cold exposure Pre-Cold SCV BAT FF%RaternMean (SD)GroupsICCagreement (95% CI)ICCconsistency (95% CI)R11063.47 (6.25)ALL.991 (.972, .998).993 (.979, .998)R263.91 (6.48)R1/R2.988 (.954, .997).990 (.960, .997)R363.28 (6.27)R1/R3.997 (.988, .999) .997 (.988, .999)Post-Cold SCV BAT FF%RaternMean (SD)GroupsICCagreement (95% CI)ICCconsistency (95% CI)R11060.64 (8.29)ALL.995 (.983, .999).997 (.990, .999)R261.20 (8.48)R1/R2.994 (.963, .999).996 (.984, .999)R360.57 (7.95)R1/R3.999 (.994, 1.000).998 (.994, 1.000)Reliability of SCV BAT R2* between three raters before and after cold exposure Pre-Cold SCV BAT R2*RaternMean (SD)GroupsICCagreement (95% CI)ICCconsistency (95% CI)R11078.11 (8.79)ALL.917 (.784, .976).913 (.771, .975)R276.88 (9.92)R1/R2.881 (.612, .969).878 (.586, .968)R377.29 (8.89)R1/R3.979 (.919, .995).982 (.929, .995)Post-Cold SCV BAT R2*RaternMean (SD)GroupsICCagreement (95% CI)ICCconsistency (95% CI)R11083.97 (15.55)ALL.970 (.917, .992).970 (.914, .992)R283.16 (16.48)R1/R2.976 (.912, .994).975 (.903, .994)R382.15 (17.71)R1/R3.969 (.884, .992).972 (.893, .993)Reliability of SCV BAT Volume between three raters before and after cold exposure Pre-Cold SCV VolumeRaternMean (SD)GroupsICCagreement (95% CI)ICCconsistency (95% CI)R11077.85 (42.62)ALL.987 (.964, .996).987 (.963, .996)R274.79 (45.05)R1/R2.980 (.927, .995).981 (.925, .995)R376.08 (41.67)R1/R3.995 (.982, .999).996 (.983, .999)Post-Cold SCV VolumeRaternMean (SD)GroupsICCagreement (95% CI)ICCconsistency (95% CI)R11077.76 (45.12)ALL.985 (.954, .996).987 (.963, .996)R274.15 (45.78)R1/R2.984 (.937, .996).985 (.942, .996)R379.83 (49.28)R1/R3.984 (.942, .996).984 (.936, .996)Relationship between T2* Reduction and Known Covariates Relationship between T2* reduction and age (r = -0.20; p = 0.2501)Relationship between T2* reduction and % body fat (r = -0.30; p = 0.0920)T2* reduction and sexVariableNMean (SD)p-valueMean DifferenceT2* Reduction Male230.95 (0.99).3190.33Female130.63 (0.67)T2* reduction and outdoor temperatureOutdoor TemperatureVariableN1 hour24 hours7 daysrp-valuerp-valuerp-valueT2* Reduction340.060.73900.050.7606-0.070.7024Evaluation of Cold Exposure Protocol in Stimulating BAT Activity Measures of cold exposure parameters to test standardization between individuals VariableNMean (SD)Mean Differencep-valueDelta MSTBMI < 25.021-4.57 (.72).33.222BMI ≥ 25.013-4.90 (.80)Male21-4.58 (.75).29.287Female13-4.87 (.76)Delta Inlet/Outlet TempBMI < 25.0211.52 (.22)-.02.759BMI ≥ 25.0131.55 (.14)Male181.57 (.18).11.145Female131.47 (.21)Interpretation of BAT MR OutcomesComparison of BAT MR outcomesBAT MR OutcomeMechanismAdvantagesLimitationsAssociationsAge(r)Sex(r)Adiposity(r)Outdoor Temp(r)Pre-Cold FF%- Quantification of TG content - BAT (lower lipid content and higher water content)- BAT (lower FF values)- no cold exposure- lower FF are reflective of browner phenotype- signal is not specific to BAT- no measurement of BAT activity- influenced by previously activated BAT+ (0.54)x+(0.83)xPre-Cold T2*- Quantification of iron/mitochondrial content- BAT (more iron-rich mitochondria)- BAT (lower T2* values)- no cold exposure- lower T2* are reflective of browner phenotype- signal is not specific to BAT - no measurement of BAT activity- influenced by previously activated BAT+ (0.42)x+(0.58)xFF% Reduction- Change in TG content after cold exposure- BAT (uses endogenous FFA during activation)- BAT (decline in FF%)- direct measure of BAT-induced thermogenesis- require cold exposure- limited studies in adult humans- affected by blood perfusion and TG delivery- (0.39)x-(0.64)xT2* Reduction- Change in deoxyHb:oxyHb after cold exposure- BAT (uses oxygen during activation)- BAT (decline in T2*)-surrogate measure of BAT-induced perfusion- require cold exposure- limited studies in adult humans- affected by temperature and magnetic field strength - more susceptible to motion artefacts xxxxBIBLIOGRAPHYADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1.Betz, M. 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