Brown Fat As a Therapy for Obesity and Diabetes

Overview

Journal Curr Opin Endocrinol Diabetes Obes

Specialty Endocrinology

Date 2010 Feb 18

PMID 20160646

Citations 190

Authors

Aaron M Cypess

C Ronald Kahn

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Human fat consists of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. This review evaluates the recent discoveries regarding the identification of functional BAT in adult humans and its potential as a therapy for obesity and diabetes.

Recent Findings: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry, and gene and protein expression assays to prove conclusively that adult humans have functional BAT. This has occurred against a backdrop of basic studies defining the origins of BAT, new components of its transcriptional regulation, and the role of hormones in stimulation of BAT growth and differentiation.

Summary: Adult humans have functional BAT, a new target for antiobesity and antidiabetes therapies focusing on increasing energy expenditure. Future studies will refine the methodologies used to measure BAT mass and activity, expand our knowledge of critical-control points in BAT regulation, and focus on testing pharmacological agents that increase BAT thermogenesis and help achieve long-lasting weight loss and an improved metabolic profile.

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References

Huttunen P, Hirvonen J, Kinnula V . The occurrence of brown adipose tissue in outdoor workers. Eur J Appl Physiol Occup Physiol. 1981; 46(4):339-45. DOI: 10.1007/BF00422121. View

Tseng Y, Kokkotou E, Schulz T, Huang T, Winnay J, Taniguchi C . New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008; 454(7207):1000-4. PMC: 2745972. DOI: 10.1038/nature07221. View

Cypess A, Lehman S, Williams G, Tal I, Rodman D, Goldfine A . Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009; 360(15):1509-17. PMC: 2859951. DOI: 10.1056/NEJMoa0810780. View

Arkan M, Hevener A, Greten F, Maeda S, Li Z, Long J . IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005; 11(2):191-8. DOI: 10.1038/nm1185. View

Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J . High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009; 58(7):1526-31. PMC: 2699872. DOI: 10.2337/db09-0530. View

Guerra C, Koza R, Yamashita H, Walsh K, Kozak L . Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest. 1998; 102(2):412-20. PMC: 508900. DOI: 10.1172/JCI3155. View

Tobin J, Celeste A . Bone morphogenetic proteins and growth differentiation factors as drug targets in cardiovascular and metabolic disease. Drug Discov Today. 2006; 11(9-10):405-11. DOI: 10.1016/j.drudis.2006.03.016. View

Shen J, Huang L, Li L, Jorgez C, Matzuk M, Brown C . Deficiency of growth differentiation factor 3 protects against diet-induced obesity by selectively acting on white adipose. Mol Endocrinol. 2008; 23(1):113-23. PMC: 2646597. DOI: 10.1210/me.2007-0322. View

Melnikova I, Wages D . Anti-obesity therapies. Nat Rev Drug Discov. 2006; 5(5):369-70. DOI: 10.1038/nrd2037. View

10.

English J, Patel S, FLANAGAN M . Association of pheochromocytomas with brown fat tumors. Radiology. 1973; 107(2):279-81. DOI: 10.1148/107.2.279. View

11.

Cinti S . The adipose organ. Prostaglandins Leukot Essent Fatty Acids. 2005; 73(1):9-15. DOI: 10.1016/j.plefa.2005.04.010. View

12.

Zingaretti M, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B . 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(9):3113-20. DOI: 10.1096/fj.09-133546. View

13.

Mori K, Yahata K, Mukoyama M, Suganami T, Makino H, Nagae T . Disruption of klotho gene causes an abnormal energy homeostasis in mice. Biochem Biophys Res Commun. 2000; 278(3):665-70. DOI: 10.1006/bbrc.2000.3864. View

14.

Lowell B, Hamann A, Lawitts J, Himms-Hagen J, Boyer B, Kozak L . Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993; 366(6457):740-2. DOI: 10.1038/366740a0. View

15.

Tseng Y, Butte A, Kokkotou E, Yechoor V, Taniguchi C, Kriauciunas K . Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin. Nat Cell Biol. 2005; 7(6):601-11. DOI: 10.1038/ncb1259. View

16.

Shekelle P, Hardy M, Morton S, Maglione M, Mojica W, Suttorp M . Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA. 2003; 289(12):1537-45. DOI: 10.1001/jama.289.12.1537. View

17.

Rothwell N, Stock M . Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci (Lond). 1983; 64(1):19-23. DOI: 10.1042/cs0640019. View

18.

Ghorbani M, Claus T, Himms-Hagen J . Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a beta3-adrenoceptor agonist. Biochem Pharmacol. 1997; 54(1):121-31. DOI: 10.1016/s0006-2952(97)00162-7. View

19.

Clapham J, Arch J . Thermogenic and metabolic antiobesity drugs: rationale and opportunities. Diabetes Obes Metab. 2007; 9(3):259-75. DOI: 10.1111/j.1463-1326.2006.00608.x. View

20.

Cunningham S, Leslie P, Hopwood D, Illingworth P, Jung R, Nicholls D . The characterization and energetic potential of brown adipose tissue in man. Clin Sci (Lond). 1985; 69(3):343-8. DOI: 10.1042/cs0690343. View