Brown adipose tissue activation is inversely related to central obesity and metabolic parameters in adult human

Qidi Wang, Min Zhang, Min Xu, Weiqiong Gu, Yun Xi, Lu Qi, Biao Li, Weiqing Wang, Qidi Wang, Min Zhang, Min Xu, Weiqiong Gu, Yun Xi, Lu Qi, Biao Li, Weiqing Wang

Abstract

Background: Recent studies have shown that adult human possess active brown adipose tissue (BAT), which might be important in affecting obesity. However, the supporting evidence on the relationship between BAT and central obesity and metabolic profile in large population based studies is sparse.

Methodology/principal findings: We studied 4011 (2688 males and 1323 females) tumor-free Chinese adults aged 18-89 for BAT activities, visceral/subcutaneous fat areas (VFA/SFA), waist circumferences (WC) and metabolic parameters. We found that the prevalence of BAT was around 2.7% in our study participants, with a significant sexual difference (5.5% in the females vs. 1.3% in the males; p<0.0001). BAT detection was increased in low temperature and declined in elderly subjects. The BAT positive subjects had lower BMI (P<0.0001), less SFA (P<0.01), VFA (P<0.0001), WC (P<0.0001), lower fasting glucose and triglyceride levels (both P<0.01) and increased HDL cholesterol concentrations (P<0.0001), compared with the BAT negative subjects. Robust logistic regression revealed that after adjustment for covariates (including age, sex, BMI, VFA, SFA and WC), age and BMI in the males (0.92 [95%CI, 0.88-0.96] and 0.84 [95% CI, 0.75-0.96], both P ≤0.008) while age and VFA in the females (0.87 [95%CI, 0.83-0.91] and 0.98 [95%CI, 0.97-0.99], respectively, P<0.05) were independently associated with detectable BAT.

Conclusions/significance: Our data suggest that decreased amount of active BAT might be associated with accumulation of visceral fat content and unfavorable metabolic outcomes.

Conflict of interest statement

Competing Interests: FAT SCAN software was kindly provided by Otsuka Pharmaceutical Co., Ltd. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Correlation between the prevalence of…
Fig 1. Correlation between the prevalence of badipose tissue and temperature, age and gender.
Panel A shows the prevalence of detectable BAT in men and women. Panel B shows the percentage of patients in different age ranges that had detectable BAT. In panel C, for the patients with detectable BAT, the activity of BAT in grams times the mean standardized uptake value (SUV) in grams per milliliter was shown in each month during a 3 year period from May 2007-Feb 2010. In Panel D, outdoor temperatures in Shanghai for the dates of scans were obtained and the percentage of subjects with detectable BAT in different temperature ranges was determined. A univariate analysis was used to assess the significance of differences in the percentages with the use of a chi-square test.
Fig 2. The prevalence of brown adipose…
Fig 2. The prevalence of brown adipose tissue was inversely related with adiposity.
Body-mass-index (the weight in kilograms divided by the square of the height in meters, panel A), Waist Circumferences (panel B), Subcutaneous Fat Areas (Panel C), Visceral Fat Areas (Panel D). The percentage of patients in each group (shown as BMI

Fig 3. The prevalence of brown adipose…

Fig 3. The prevalence of brown adipose tissue was nversely related with metabolic parameters.

Fasting…

Fig 3. The prevalence of brown adipose tissue was nversely related with metabolic parameters.
Fasting plasma glucose (Panel A), triglycerides (Panel B) and total cholesterol (Panel C) levels were divided into thirds. The percentage of patients in each subgroup who had detectable BAT was shown, and the P values for trend were calculated by using Mantel-Haenszel Chi-Square test.
Fig 3. The prevalence of brown adipose…
Fig 3. The prevalence of brown adipose tissue was nversely related with metabolic parameters.
Fasting plasma glucose (Panel A), triglycerides (Panel B) and total cholesterol (Panel C) levels were divided into thirds. The percentage of patients in each subgroup who had detectable BAT was shown, and the P values for trend were calculated by using Mantel-Haenszel Chi-Square test.

References

    1. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004; 84: 277–359.
    1. Hany TF, Gharehpapagh E, Kamel EM, Buck A, Himms-Hagen J, von Schulthess GK.. Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med Mol Imaging. 2002; 29: 1393–1398.
    1. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009; 360: 1509–1517. 10.1056/NEJMoa0810780
    1. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009; 360: 1500–1508. 10.1056/NEJMoa0808718
    1. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009; 360: 1518–1525. 10.1056/NEJMoa0808949
    1. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014; 156: 20–44. 10.1016/j.cell.2013.12.012
    1. Spiegelman BM. Banting Lecture 2012: Regulation of adipogenesis: toward new therapeutics for metabolic disease. Diabetes. 2013; 62: 1774–1782. 10.2337/db12-1665
    1. Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med. 2013; 19: 635–639. 10.1038/nm.3112
    1. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012; 150: 366–376. 10.1016/j.cell.2012.05.016
    1. Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2011; 121: 96–105. 10.1172/JCI44271
    1. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481: 463–468. 10.1038/nature10777
    1. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009; 58: 1526–1531. 10.2337/db09-0530
    1. Yoneshiro T, Saito M. Activation and recruitment of brown adipose tissue as anti-obesity regimens in humans. Ann Med. 2014; 5: 1–9.
    1. Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, et al. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes. 2014; 63(11): 3686–3698. 10.2337/db14-0513
    1. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011; 17: 200–205. 10.1038/nm.2297
    1. Boyko EJ, Fujimoto WY, Leonetti DL, Newell-Morris L. Visceral adiposity and risk of type 2 diabetes: a prospective study among Japanese Americans. Diabetes Care. 2000; 23: 465–471.
    1. Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J (Clin Res Ed). 1984; 288: 1401–1404.
    1. Kanaya AM, Harris T, Goodpaster BH, Tylavsky F, Cummings SR. Adipocytokines attenuate the association between visceral adiposity and diabetes in older adults. Diabetes Care. 2004; 27: 1375–1380.
    1. Donahue RP, Abbott RD. Central obesity and coronary heart disease in men. Lancet. 1987; 2: 1215
    1. Despres JP, Tremblay A, Theriault G, Perusse L, Leblanc C, Bouchard C. Relationships between body fatness, adipose tissue distribution and blood pressure in men and women. J Clin Epidemiol. 1988; 41: 889–897.
    1. Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, et al. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS One. 2011; 6: e21006 10.1371/journal.pone.0021006
    1. Volume Viewer 2 User Guide. GE Medical Systems 5135930—100 Revision 2. 2005. pp. 399–401.
    1. Yoshizumi T, Nakamura T, Yamane M, Islam AH, Menju M, Yamasaki K, et al. Abdominal fat: standardized technique for measurement at CT. Radiology. 1999; 211: 283–286.
    1. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995; 854: 1–452.
    1. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001; 285: 2486–2497.
    1. Zukotynski KA, Fahey FH, Laffin S, Davis R, Treves ST, Grant FD, et al. Seasonal variation in the effect of constant ambient temperature of 24 degrees C in reducing FDG uptake by brown adipose tissue in children. Eur J Nucl Med Mol Imaging. 2010; 37: 1854–1860. 10.1007/s00259-010-1485-2
    1. Browning LM, Hsieh SD, Ashwell M. A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value. Nutr Res Rev. 2010; 23: 247–269. 10.1017/S0954422410000144
    1. Bray GA. Obesity: the disease. J Med Chem. 2006; 49: 4001–4007.
    1. Kozak LP. Brown fat and the myth of diet-induced thermogenesis. Cell Metab. 2010; 11: 263–267. 10.1016/j.cmet.2010.03.009
    1. Lowell BB, V SS, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993; 366: 740–742.
    1. Zhang Q, Ye H, Miao Q, Zhang Z, Wang Y, Zhu X, et al. Differences in the metabolic status of healthy adults with and without active brown adipose tissue. Wien Klin Wochenschr. 2013; 125: 687–695. 10.1007/s00508-013-0431-2
    1. Matsushita M, Yoneshiro T, Aita S, Kameya T, Sugie H, Saito M. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes (Lond). 2014; 38: 812–817. 10.1038/ijo.2013.206
    1. Lee P, Greenfield JR, Ho KK, Fulham MJ. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2010; 299: E601–606. 10.1152/ajpendo.00298.2010
    1. Stefan N, Pfannenberg C, Haring HU. The importance of brown adipose tissue. N Engl J Med. 2009; 361: 416–417; author reply 418–421.
    1. Au-Yong IT, Thorn N, Ganatra R, Perkins AC, Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes. 2009; 58: 2583–2587. 10.2337/db09-0833
    1. Zhang Z, Cypess AM, Miao Q, Ye H, Liew CW, Zhang Q, et al. The prevalence and predictors of active brown adipose tissue in Chinese adults. Eur J Endocrinol. 2014; 170: 359–366. 10.1530/EJE-13-0712
    1. Bakker LE, Boon MR, van der Linden RA, Arias-Bouda LP, van Klinken JB, Smit F, et al. Brown adipose tissue volume in healthy lean south Asian adults compared with white Caucasians: a prospective, case-controlled observational study. Lancet Diabetes Endocrinol. 2014; 2: 210–217. 10.1016/S2213-8587(13)70156-6
    1. Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009; 23: 3113–3120. 10.1096/fj.09-133546
    1. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, et al. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring). 2011; 19: 1755–1760. 10.1038/oby.2011.125
    1. Coppack SW, Jensen MD, Miles JM. In vivo regulation of lipolysis in humans. J Lipid Res. 1994; 35: 177–193.
    1. Dulloo AG, Miller DS. Energy balance following sympathetic denervation of brown adipose tissue. Can J Physiol Pharmacol. 1984; 62: 235–240.
    1. Hamann A, Flier JS, Lowell BB. Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia. Endocrinology. 1996; 137: 21–29.
    1. Nakayama K, Miyashita H, Yanagisawa Y, Iwamoto S. Seasonal effects of UCP1 gene polymorphism on visceral fat accumulation in Japanese adults. PLoS One. 2013; 8: e74720 10.1371/journal.pone.0074720
    1. Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism. 1991; 40: 1323–1326.
    1. Espeland MA, Stefanick ML, Kritz-Silverstein D, Fineberg SE, Waclawiw MA, James MK, et al. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators. J Clin Endocrinol Metab. 1997; 82: 1549–1556.
    1. Martinez de Morentin PB, Gonzalez-Garcia I, Martins L, Lage R, Fernandez-Mallo D, Martínez-Sánchez N, et al. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab. 2014; 20: 41–53. 10.1016/j.cmet.2014.03.031
    1. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009; 9: 203–209. 10.1016/j.cmet.2008.12.014
    1. Kontani Y, Wang Y, Kimura K, Inokuma KI, Saito M, Suzuki-Miura T, et al. UCP1 deficiency increases susceptibility to diet-induced obesity with age. Aging Cell. 2005; 4: 147–155.
    1. Nedergaard J, Bengtsson T, Cannon B. Three years with adult human brown adipose tissue. Ann N Y Acad Sci. 2010; 1212: E20–36. 10.1111/j.1749-6632.2010.05905.x
    1. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013; 19: 1252–1263. 10.1038/nm.3361

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