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      Brown Adipose Tissue in Morbidly Obese Subjects

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          Abstract

          Background

          Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure.

          Methods and Findings

          After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans.

          Conclusions

          This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity.

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          Most cited references12

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          Distribution and development of brown adipocytes in the murine and human adipose organ.

          Murine white and brown adipocytes are found together in dissectible visceral and subcutaneous fat depots supplied by specific vessels and nerves, forming a multi-depot organ with plastic properties. Many of the anatomo-physiological features of murine fat depots apply to humans. 2010 Elsevier Inc. All rights reserved.
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            Impact of Age on the Relationships of Brown Adipose Tissue With Sex and Adiposity in Humans

            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. RESEARCH DESIGN AND METHODS Data from 260 subjects (98 with BAT and 162 study date–matched control subjects) who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body. RESULTS 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 ≤ 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 rs = −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 ≤ 0.09). CONCLUSIONS 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.
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              The distribution of brown adipose tissue in the human.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                24 February 2011
                : 6
                : 2
                : e17247
                Affiliations
                [1 ]Department of Human Biology, School for Nutrition and Toxicology and Metabolism - NUTRIM, Maastricht University, Maastricht, The Netherlands
                [2 ]Department of General Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
                [3 ]Department of Nuclear Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
                University of Padova, Medical School, Italy
                Author notes

                Conceived and designed the experiments: GV NB GJT BB PS WvML. Performed the experiments: GV WvML. Analyzed the data: GV WvML. Contributed reagents/materials/analysis tools: GV NB GJT BB PS WvML. Wrote the manuscript: GV NB GJT BB PS WvML. Involved in the data collection: GV WvML. Prepared the first draft of manuscript: GV. Principal investigator: WvML. Reviewed the paper: WvML NB GJT BB PS. Approved the paper for publication: GV NB GJT BB PS WvML.

                Article
                PONE-D-10-05659
                10.1371/journal.pone.0017247
                3044745
                21390318
                c7ec865e-6ee4-4716-8cd5-6a4a2088b8d9
                Vijgen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 25 November 2010
                : 23 January 2011
                Page count
                Pages: 6
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Physiological Processes
                Energy Metabolism
                Biochemistry
                Cytochemistry
                Energy-Producing Processes
                Lipids
                Fats
                Medicine
                Anatomy and Physiology
                Physiological Processes
                Energy Metabolism
                Endocrinology
                Endocrine Physiology
                Nutrition
                Obesity
                Radiology
                Nuclear Medicine

                Uncategorized
                Uncategorized

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