Mechanisms in endocrinology: Brown adipose tissue in humans: Regulation and metabolic significance

European Journal of Endocrinology

Volumn 175, Issue 1, 2016, Pages R11-R25

  Thuzar, Moe ^a,b   Ho, Ken K Y ^a,b  

^a PRINCESS ALEXANDRA HOSPITAL   (Australia)

^b UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CATECHOLAMINE; GLUCOCORTICOID; INSULIN; IRISIN; MINERALOCORTICOID; SEX HORMONE; THYROID HORMONE;

BODY FAT; BROWN ADIPOCYTE; BROWN ADIPOSE TISSUE; CELL DIFFERENTIATION; CELL PROLIFERATION; COLD EXPOSURE; EXERCISE; GLYCATION; HUMAN; INSULIN SENSITIVITY; METABOLIC REGULATION; NONHUMAN; OBESITY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYMPATHETIC NERVE; THERMOGENESIS; WHITE ADIPOSE TISSUE; DIET; ENERGY METABOLISM; METABOLISM; PHYSIOLOGY; TEMPERATURE;

ADIPOCYTES, BROWN; ADIPOSE TISSUE, BROWN; DIET; ENERGY METABOLISM; HUMANS; INSULIN; OBESITY; TEMPERATURE; THERMOGENESIS;

EID: 84978969880     PISSN: 08044643     EISSN: 1479683X     Source Type: Journal    
DOI: 10.1530/EJE-15-1217     Document Type: Review

References (163)

1. Cannon B & Nedergaard J. Brown adipose tissue: function and physiological significance. Physiological Reviews 2004 84 277-359. (doi:10.1152/physrev.00015.2003)
2. Lee P, Zhao JT, Swarbrick MM, Gracie G, Bova R, Greenfield JR, Freund J & Ho KK. High prevalence of brown adipose tissue in adult humans. Journal of Clinical Endocrinology and Metabolism 2011 96 2450-2455. (doi:10.1210/jc.2011-0487)
3. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P & Teule GJ. Cold-activated brown adipose tissue in healthy men. New England Journal of Medicine 2009 360 1500-1508. (doi:10.1056/NEJMoa0808718)
4. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S et al. Functional brown adipose tissue in healthy adults. New England Journal of Medicine 2009 360 1518-1525. (doi:10.1056/NEJMoa0808949)
5. Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, Nedergaard J & Cinti S. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB Journal 2009 23 3113-3120. (doi:10.1096/fj.09-133546)
6. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B & Nedergaard J. Chronic peroxisome proliferator-activated receptor γ (PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. Journal of Biological Chemistry 2010 285 7153-7164. (doi:10.1074/jbc. M109.053942)
7. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008 454 961-967. (doi:10.1038/nature07182)
8. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012 150 366-376. (doi:10.1016/j.cell.2012.05.016)
9. Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. PNAS 2007 104 4401-4406. (doi:10.1073/pnas.0610615104)
10. Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, Giacobino JP, De Matteis R & Cinti S. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. American Journal of Physiology. Endocrinology and Metabolism 2010 298 E1244-E1253. (doi:10.1152/ajpendo.00600.2009)
11. Young P, Arch JR & Ashwell M. Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Letters 1984 167 10-14. (doi:10.1016/0014-5793(84)80822-4)
12. Walden TB, Hansen IR, Timmons JA, Cannon B & Nedergaard J. Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues. American Journal of Physiology. Endocrinology and Metabolism 2012 302 E19-E31. (doi:10.1152/ajpendo.00249.2011)
13. Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, Huang TL, Roberts-Toler C, Weiner LS, Sze C et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nature Medicine 2013 19 635-639. (doi:10.1038/nm.3112)
14. Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P et al. Evidence for two types of brown adipose tissue in humans. Nature Medicine 2013 19 631-634. (doi:10.1038/nm.3017)
15. Jespersen NZ, Larsen TJ, Peijs L, Daugaard S, Homoe P, Loft A, de Jong J, Mathur N, Cannon B, Nedergaard J et al. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metabolism 2013 17 798-805. (doi:10.1016/j.cmet.2013.04.011)
16. Himms-Hagen J, Melnyk A, Zingaretti MC, Ceresi E, Barbatelli G & Cinti S. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. American Journal of Physiology. Cell Physiology 2000 279 C670-C681.
17. Lee YH, Petkova AP, Mottillo EP & Granneman JG. In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding. Cell Metabolism 2012 15 480-491. (doi:10.1016/j.cmet.2012.03.009)
18. Wang QA, Tao C, Gupta RK & Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nature Medicine 2013 19 1338-1344. (doi:10.1038/nm.3324)
19. Bukowiecki L, Collet AJ, Follea N, Guay G & Jahjah L. Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia. American Journal of Physiology 1982 242 E353-E359.
20. Bukowiecki LJ, Geloen A & Collet AJ. Proliferation and differentiation of brown adipocytes from interstitial cells during cold acclimation. American Journal of Physiology 1986 250 C880-C887.
21. Blondin DP, Labbe SM, Tingelstad HC, Noll C, Kunach M, Phoenix S, Guerin B, Turcotte EE, Carpentier AC, Richard D et al. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. Journal of Clinical Endocrinology and Metabolism 2014 99 E438-E446. (doi:10.1210/jc.2013-3901)
22. Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, Werner CD, Chen KY & Celi FS. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes 2014 63 3686-3698. (doi:10.2337/db14-0513)
23. van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, Hansen J, Jorgensen JA, Wu J, Mottaghy FM et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. Journal of Clinical Investigation 2013 123 3395-3403. (doi:10.1172/JCI68993)
24. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T & Saito M. Recruited brown adipose tissue as an antiobesity agent in humans. Journal of Clinical Investigation 2013 123 3404-3408. (doi:10.1172/JCI67803)
25. Au-Yong IT, Thorn N, Ganatra R, Perkins AC & Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes 2009 58 2583-2587. (doi:10.2337/db09-0833)
26. Huang YC, Hsu CC, Wang PW, Chang YH, Chen TB, Lee BF & Chiu NT. Review analysis of the association between the prevalence of activated brown adipose tissue and outdoor temperature. Scientific World Journal 2012 2012 793039. (doi:10.1100/2012/793039)
27. Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC & Richard D. 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. Journal of Clinical Endocrinology and Metabolism 2011 96 192-199. (doi:10.1210/jc.2010-0989)
28. Persichetti A, Sciuto R, Rea S, Basciani S, Lubrano C, Mariani S, Ulisse S, Nofroni I, Maini CL & Gnessi L. Prevalence, mass, and glucose-uptake activity of (1)(8)F-FDG-detected brown adipose tissue in humans living in a temperate zone of Italy. PLoS ONE 2013 8 e63391. (doi:10.1371/journal.pone.0063391)
29. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K 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. (doi:10.2337/db09-0530)
30. Christensen CR, Clark PB & Morton KA. Reversal of hypermetabolic brown adipose tissue in F-18 FDG PET imaging. Clinical Nuclear Medicine 2006 31 193-196. (doi:10.1097/01.rlu.0000204199. 33136.05)
31. Garcia CA, Van Nostrand D, Atkins F, Acio E, Butler C, Esposito G, Kulkarni K & Majd M. Reduction of brown fat 2-deoxy-2-[F-18]fluoro-D-glucose uptake by controlling environmental temperature prior to positron emission tomography scan. Molecular Imaging and Biology 2006 8 24-29. (doi:10.1007/s11307-005-0030-3)
32. Zukotynski KA, Fahey FH, Laffin S, Davis R, Treves ST, Grant FD & Drubach LA. Constant ambient temperature of 24 degrees C significantly reduces FDG uptake by brown adipose tissue in children scanned during the winter. European Journal of Nuclear Medicine and Molecular Imaging 2009 36 602-606. (doi:10.1007/s00259-008-0983-y)
33. Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, Haman F, Turcotte EE, Richard D & Carpentier AC. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. Journal of Clinical Investigation 2012 122 545-552. (doi:10.1172/JCI60433)
34. Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J & Granneman JG. 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. Journal of Nuclear Medicine 2013 54 523-531. (doi:10.2967/jnumed.112.111336)
35. Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, Scheinin M, Taittonen M, Niemi T, Enerback S et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metabolism 2011 14 272-279. (doi:10.1016/j.cmet.2011.06.012)
36. Huttunen P, Hirvonen J & Kinnula V. The occurrence of brown adipose tissue in outdoor workers. European Journal of Applied Physiology and Occupational Physiology 1981 46 339-345. (doi:10.1007/BF00422121)
37. Hanssen MJ, Hoeks J, Brans B, van der Lans AA, Schaart G, van den Driessche JJ, Jorgensen JA, Boekschoten MV, Hesselink MK, Havekes B et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nature Medicine 2015 21 863-865. (doi:10.1038/nm.3891)
38. Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, Herscovitch P, Millo CM, Remaley A, Lee P et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. Journal of Clinical Endocrinology and Metabolism 2013 98 E1218-E1223. (doi:10.1210/jc.2012-4213)
39. Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O, Holman AR, Tal I, Palmer MR, Kolodny GM et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo. PNAS 2012 109 10001-10005. (doi:10.1073/pnas.1207911109)
40. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metabolism 2014 19 302-309. (doi:10.1016/j.cmet.2013. 12.017)
41. Vosselman MJ, Brans B, van der Lans AA, Wierts R, van Baak MA, Mottaghy FM, Schrauwen P & van Marken Lichtenbelt WD. Brown adipose tissue activity after a high-calorie meal in humans. American Journal of Clinical Nutrition 2013 98 57-64. (doi:10.3945/ajcn.113. 059022)
42. Shimizu Y, Nikami H, Tsukazaki K, Machado UF, Yano H, Seino Y & Saito M. Increased expression of glucose transporter GLUT-4 in brown adipose tissue of fasted rats after cold exposure. American Journal of Physiology 1993 264 E890-E895.
43. Cinti S. Between brown and white: novel aspects of adipocyte differentiation. Annals of Medicine 2011 43 104-115. (doi:10.3109/07853890.2010.535557)
44. Fukuchi K, Tatsumi M, Ishida Y, Oku N, Hatazawa J & Wahl RL. Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma. Experimental and Clinical Endocrinology & Diabetes 2004 112 601-603. (doi:10.1055/s-2004-830407)
45. Hadi M, Chen CC, Whatley M, Pacak K & Carrasquillo JA. Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. Journal of Nuclear Medicine 2007 48 1077-1083. (doi:10.2967/jnumed.106.035915)
46. Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, Li B & Wang W. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS ONE 2011 6 e21006. (doi:10.1371/journal.pone.0021006)
47. Frontini A, Vitali A, Perugini J, Murano I, Romiti C, Ricquier D, Guerrieri M & Cinti S. White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochimica et Biophysica Acta 2013 1831 950-959. (doi:10.1016/j.bbalip.2013. 02.005)
48. Lean ME, James WP, Jennings G & Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. International Journal of Obesity 1986 10 219-227.
49. Ricquier D, Nechad M & Mory G. Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma. Journal of Clinical Endocrinology and Metabolism 1982 54 803-807. (doi:10.1210/jcem-54-4-803)
50. Collins S, Yehuda-Shnaidman E & Wang H. Positive and negative control of Ucp1 gene transcription and the role of β-adrenergic signaling networks. International Journal of Obesity 2010 34 (Suppl 1) S28-S33. (doi:10.1038/ijo.2010.180)
51. Shimizu Y, Nikami H & Saito M. Sympathetic activation of glucose utilization in brown adipose tissue in rats. Journal of Biochemistry 1991 110 688-692.
52. Deng C, Paoloni-Giacobino A, Kuehne F, Boss O, Revelli JP, Moinat M, Cawthorne MA, Muzzin P & Giacobino JP. Respective degree of expression of β 1-, β 2- and β 3-adrenoceptors in human brown and white adipose tissues. British Journal of Pharmacology 1996 118 929-934. (doi:10.1111/j.1476-5381.1996.tb15488.x)
53. Mattsson CL, Csikasz RI, Chernogubova E, Yamamoto DL, Hogberg HT, Amri EZ, Hutchinson DS & Bengtsson T. β(1)-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β(3)-adrenergic receptor-knockout mice via nonshivering thermogenesis. American Journal of Physiology. Endocrinology and Metabolism 2011 301 E1108-E1118. (doi:10.1152/ajpendo.00085.2011)
54. Muzzin P, Revelli JP, Kuhne F, Gocayne JD, McCombie WR, Venter JC, Giacobino JP & Fraser CM. An adipose tissue-specific β-adrenergic receptor. Molecular cloning and down-regulation in obesity. Journal of Biological Chemistry 1991 266 24053-24058.
55. Puigserver P, Pico C, Stock MJ & Palou A. Effect of selective β-adrenoceptor stimulation on UCP synthesis in primary cultures of brown adipocytes. Molecular and Cellular Endocrinology 1996 117 7-16. (doi:10.1016/0303-7207(95)03727-6)
56. Parysow O, Mollerach AM, Jager V, Racioppi S, San Roman J & Gerbaudo VH. Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans. Clinical Nuclear Medicine 2007 32 351-357. (doi:10.1097/01.rlu.0000259570. 69163.04)
57. Soderlund V, Larsson SA & Jacobsson H. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol. European Journal of Nuclear Medicine and Molecular Imaging 2007 34 1018-1022. (doi:10.1007/s00259-006-0318-9)
58. Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A et al. Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metabolism 2015 21 33-38. (doi:10.1016/j.cmet.2014.12.009)
59. Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiological Reviews 2006 86 435-464. (doi:10.1152/physrev. 00009.2005)
60. Lee JY, Takahashi N, Yasubuchi M, Kim YI, Hashizaki H, Kim MJ, Sakamoto T, Goto T & Kawada T. Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. American Journal of Physiology. Cell Physiology 2012 302 C463-C472. (doi:10.1152/ajpcell.00010.2011)
61. Rothwell NJ, Stock MJ & Sudera DK. Changes in adrenoreceptor density in brown adipose tissue from hyperthyroid rats. European Journal of Pharmacology 1985 114 227-229. (doi:10.1016/0014-2999 (85)90632-6)
62. Rubio A, Raasmaja A, Maia AL, Kim KR & Silva JE. Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. β 1- and β 2-adrenergic receptors and cyclic adenosine 3′,5′-monophosphate generation. Endocrinology 1995 136 3267-3276. (doi:10.1210/endo.136.8.7628360)
63. Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nature Medicine 2010 16 1001-1008. (doi:10.1038/nm.2207)
64. Skarulis MC, Celi FS, Mueller E, Zemskova M, Malek R, Hugendubler L, Cochran C, Solomon J, Chen C & Gorden P. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. Journal of Clinical Endocrinology and Metabolism 2010 95 256-262. (doi:10.1210/jc.2009-0543)
65. Lahesmaa M, Orava J, Schalin-Jantti C, Soinio M, Hannukainen JC, Noponen T, Kirjavainen A, Iida H, Kudomi N, Enerback S et al. Hyperthyroidism increases brown fat metabolism in humans. Journal of Clinical Endocrinology and Metabolism 2014 99 E28-E35. (doi:10.1210/jc.2013-2312)
66. Forrest D & Vennstrom B. Functions of thyroid hormone receptors in mice. Thyroid 2000 10 41-52. (doi:10.1089/thy.2000.10.41)
67. Ribeiro MO, Bianco SD, Kaneshige M, Schultz JJ, Cheng SY, Bianco AC & Brent GA. Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-β isoform specific and required for adaptive thermogenesis. Endocrinology 2010 151 432-440. (doi:10.1210/en.2009-0667)
68. Ribeiro MO, Carvalho SD, Schultz JJ, Chiellini G, Scanlan TS, Bianco AC & Brent GA. Thyroid hormone - sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific. Journal of Clinical Investigation 2001 108 97-105. (doi:10.1172/JCI200112584)
69. Grover GJ, Egan DM, Sleph PG, Beehler BC, Chiellini G, Nguyen NH, Baxter JD & Scanlan TS. Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3′-triiodo-L-thyronine. Endocrinology 2004 145 1656-1661. (doi:10.1210/en.2003-0973)
70. Trost SU, Swanson E, Gloss B, Wang-Iverson DB, Zhang H, Volodarsky T, Grover GJ, Baxter JD, Chiellini G, Scanlan TS et al. The thyroid hormone receptor-β-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Endocrinology 2000 141 3057-3064. (doi:10.1210/endo.141.9.7681)
71. Resmini E, Farkas C, Murillo B, Barahona MJ, Santos A, Martinez-Momblan MA, Roig O, Ybarra J, Geli C & Webb SM. Body composition after endogenous (Cushing's syndrome) and exogenous (rheumatoid arthritis) exposure to glucocorticoids. Hormone and Metabolic Research 2010 42 613-618. (doi:10.1055/s-0030-1255032)
72. Cristancho AG & Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nature Reviews. Molecular Cell Biology 2011 12 722-734. (doi:10.1038/nrm3198)
73. Christ-Crain M, Kola B, Lolli F, Fekete C, Seboek D, Wittmann G, Feltrin D, Igreja SC, Ajodha S, Harvey-White J et al. AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. FASEB Journal 2008 22 1672-1683. (doi:10.1096/fj.07-094144)
74. Feldman D. Evidence that brown adipose tissue is a glucocorticoid target organ. Endocrinology 1978 103 2091-2097. (doi:10.1210/endo-103-6-2091)
75. Galpin KS, Henderson RG, James WP & Trayhurn P. GDP binding to brown-adipose-tissue mitochondria of mice treated chronically with corticosterone. Biochemical Journal 1983 214 265-268. (doi:10.1042/bj2140265)
76. Moriscot A, Rabelo R & Bianco AC. Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue. American Journal of Physiology 1993 265 E81-E87.
77. Feve B, Baude B, Krief S, Strosberg AD, Pairault J & Emorine LJ. Inhibition by dexamethasone of β 3-adrenergic receptor responsiveness in 3T3-F442A adipocytes. Evidence for a transcriptional mechanism. Journal of Biological Chemistry 1992 267 15909-15915.
78. Kiely J, Hadcock JR, Bahouth SW & Malbon CC. Glucocorticoids down-regulate β 1-adrenergic-receptor expression by suppressing transcription of the receptor gene. Biochemical Journal 1994 302 (Pt 2) 397-403. (doi:10.1042/bj3020397)
79. Soumano K, Desbiens S, Rabelo R, Bakopanos E, Camirand A & Silva JE. Glucocorticoids inhibit the transcriptional response of the uncoupling protein-1 gene to adrenergic stimulation in a brown adipose cell line. Molecular and Cellular Endocrinology 2000 165 7-15. (doi:10.1016/S0303-7207(00)00276-8)
80. Hardwick AJ, Linton EA & Rothwell NJ. Thermogenic effects of the antiglucocorticoid RU-486 in the rat: involvement of corticotropinreleasing factor and sympathetic activation of brown adipose tissue. Endocrinology 1989 124 1684-1688. (doi:10.1210/endo-124-4-1684)
81. Barclay JL, Agada H, Jang C, Ward M, Wetzig N & Ho KK. Effects of glucocorticoids on human brown adipocytes. Journal of Endocrinology 2015 224 139-147. (doi:10.1530/JOE-14-0538)
82. Caprio M, Feve B, Claes A, Viengchareun S, Lombes M & Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB Journal 2007 21 2185-2194. (doi:10.1096/fj.06-7970com)
83. Bochud M, Nussberger J, Bovet P, Maillard MR, Elston RC, Paccaud F, Shamlaye C & Burnier M. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension 2006 48 239-245. (doi:10.1161/01.HYP.0000231338.41548.fc)
84. Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M, Rabbia F, Federspil G & Mulatero P. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. Journal of Clinical Endocrinology and Metabolism 2006 91 454-459. (doi:10.1210/jc.2005-1733)
85. Giacchetti G, Ronconi V, Turchi F, Agostinelli L, Mantero F, Rilli S & Boscaro M. Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. Journal of Hypertension 2007 25 177-186. (doi:10.1097/HJH.0b013e3280108e6f)
86. Penfornis P, Viengchareun S, LeMenuet D, Cluzeaud F, Zennaro MC & Lombes M. The mineralocorticoid receptor mediates aldosteroneinduced differentiation of T37i cells into brown adipocytes. American Journal of Physiology. Endocrinology and Metabolism 2000 279 E386-E394.
87. Zennaro MC, Le Menuet D, Viengchareun S, Walker F, Ricquier D & Lombes M. Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. Journal of Clinical Investigation 1998 101 1254-1260. (doi:10.1172/JCI1915)
88. Viengchareun S, Penfornis P, Zennaro MC & Lombes M. Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes. American Journal of Physiology. Endocrinology and Metabolism 2001 280 E640-E649.
89. Armani A, Cinti F, Marzolla V, Morgan J, Cranston GA, Antelmi A, Carpinelli G, Canese R, Pagotto U, Quarta C et al. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high-fat-diet-fed mice. FASEB Journal 2014 28 3745-3757. (doi:10.1096/fj.13-245415)
90. Shi H, Seeley RJ & Clegg DJ. Sexual differences in the control of energy homeostasis. Frontiers in Neuroendocrinology 2009 30 396-404. (doi:10.1016/j.yfrne.2009.03.004)
91. Rodriguez-Cuenca S, Monjo M, Frontera M, Gianotti M, Proenza AM & Roca P. Sex steroid receptor expression profile in brown adipose tissue. Effects of hormonal status. Cellular Physiology and Biochemistry 2007 20 877-886. (doi:10.1159/000110448)
92. Pedersen SB, Bruun JM, Kristensen K & Richelsen B. Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white adipose tissue, and skeletal muscle in rats by estrogen. Biochemical and Biophysical Research Communications 2001 288 191-197. (doi:10.1006/bbrc.2001.5763)
93. Rodriguez AM, Monjo M, Roca P & Palou A. Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cellular and Molecular Life Sciences 2002 59 1714-1723. (doi:10.1007/PL00012499)
94. Rodriguez-Cuenca S, Monjo M, Gianotti M, Proenza AM & Roca P. Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17β-estradiol, testosterone, and progesterone. American Journal of Physiology. Endocrinology and Metabolism 2007 292 E340-E346. (doi:10.1152/ajpendo.00175.2006)
95. Fan W, Yanase T, Nomura M, Okabe T, Goto K, Sato T, Kawano H, Kato S & Nawata H. Androgen receptor null male mice develop lateonset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion. Diabetes 2005 54 1000-1008. (doi:10.2337/diabetes. 54.4.1000)
96. Abelenda M, Nava MP, Fernandez A & Puerta ML. Brown adipose tissue thermogenesis in testosterone-treated rats. Acta Endocrinologica 1992 126 434-437.
97. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A et al. Identification and importance of brown adipose tissue in adult humans. New England Journal of Medicine 2009 360 1509-1517. (doi:10.1056/NEJMoa0810780)
98. Lee P, Greenfield JR, Ho KK & Fulham MJ. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. American Journal of Physiology. Endocrinology and Metabolism 2010 299 E601-E606. (doi:10.1152/ajpendo.00298.2010)
99. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, Miyagawa M, Tsujisaki M & Saito M. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity 2011 19 1755-1760. (doi:10.1038/oby.2011.125)
100. Shibata H, Perusse F & Bukowiecki LJ. The role of insulin in nonshivering thermogenesis. Canadian Journal of Physiology and Pharmacology 1987 65 152-158. (doi:10.1139/y87-030)
101. Burcelin R, Kande J, Ricquier D & Girard J. Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia. Biochemical Journal 1993 291 (Pt 1) 109-113. (doi:10.1042/bj2910109)
102. Geloen A & Trayhurn P. Regulation of the level of uncoupling protein in brown adipose tissue by insulin. American Journal of Physiology 1990 258 R418-R424.
103. Ebner S, Burnol AF, Ferre P, de Saintaurin MA & Girard J. Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes. Potentiation by insulin of norepinephrineinduced glucose oxidation. European Journal of Biochemistry 1987 170 469-474. (doi:10.1111/j.1432-1033.1987.tb13723.x)
104. Marette A & Bukowiecki LJ. Stimulation of glucose transport by insulin and norepinephrine in isolated rat brown adipocytes. American Journal of Physiology 1989 257 C714-C721.
105. Guerra C, Navarro P, Valverde AM, Arribas M, Bruning J, Kozak LP, Kahn CR & Benito M. Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance. Journal of Clinical Investigation 2001 108 1205-1213. (doi:10.1172/JCI13103)
106. Muntzel MS, Anderson EA, Johnson AK & Mark AL. Mechanisms of insulin action on sympathetic nerve activity. Clinical and Experimental Hypertension 1995 17 39-50. (doi:10.3109/10641969509087053)
107. Rahmouni K, Morgan DA, Morgan GM, Liu X, Sigmund CD, Mark AL & Haynes WG. Hypothalamic PI3K and MAPK differentially mediate regional sympathetic activation to insulin. Journal of Clinical Investigation 2004 114 652-658. (doi:10.1172/JCI21737)
108. Geloen A & Trayhurn P. Regulation of the level of uncoupling protein in brown adipose tissue by insulin requires the mediation of the sympathetic nervous system. FEBS Letters 1990 267 265-267. (doi:10.1016/0014-5793(90)80941-B)
109. de Jonge L & Bray GA. The thermic effect of food and obesity: a critical review. Obesity Research 1997 5 622-631. (doi:10.1002/j.1550-8528. 1997.tb00584.x)
110. Kinabo JL & Durnin JV. Thermic effect of food in man: effect of meal composition, and energy content. British Journal of Nutrition 1990 64 37-44. (doi:10.1079/BJN19900007)
111. Westerterp KR, Wilson SA & Rolland V. Diet induced thermogenesis measured over 24h in a respiration chamber: effect of diet composition. International Journal of Obesity and Related Metabolic Disorders 1999 23 287-292. (doi:10.1038/sj.ijo.0800810)
112. Rothwell NJ & Stock MJ. A role for brown adipose tissue in dietinduced thermogenesis. Nature 1979 281 31-35. (doi:10.1038/281031a0)
113. Tulp OL, Frink R & Danforth E Jr. Effect of cafeteria feeding on brown and white adipose tissue cellularity, thermogenesis, and body composition in rats. Journal of Nutrition 1982 112 2250-2260.
114. Rothwell NJ & Stock MJ. Effect of chronic food restriction on energy balance, thermogenic capacity, and brown-adipose-tissue activity in the rat. Bioscience Reports 1982 2 543-549. (doi:10.1007/BF01314214)
115. Kozak LP. Brown fat and the myth of diet-induced thermogenesis. Cell Metabolism 2010 11 263-267. (doi:10.1016/j.cmet.2010.03.009)
116. Kawada T, Watanabe T, Takaishi T, Tanaka T & Iwai K. Capsaicin-induced β-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. Proceedings of the Society for Experimental Biology and Medicine 1986 183 250-256. (doi:10.3181/00379727-183-42414)
117. Clegg ME, Golsorkhi M & Henry CJ. Combined medium-chain triglyceride and chilli feeding increases diet-induced thermogenesis in normal-weight humans. European Journal of Nutrition 2013 52 1579-1585. (doi:10.1007/s00394-012-0463-9)
118. Yoshioka M, St-Pierre S, Suzuki M & Tremblay A. Effects of red pepper added to high-fat and high-carbohydrate meals on energymetabolism and substrate utilization in Japanese women. British Journal of Nutrition 1998 80 503-510.
119. Yoneshiro T & Saito M. Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management. Current Opinion in Clinical Nutrition and Metabolic Care 2013 16 625-631. (doi:10.1097/MCO.0b013e3283653ee1)
120. Leung FW. Capsaicin as an anti-obesity drug. Progress in Drug Research 2014 68 171-179.
121. Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, Yan ZC, Wang LJ, Zhao ZG, Zhu SJ et al. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circulation Research 2007 100 1063-1070. (doi:10.1161/01.RES. 0000262653.84850.8b)
122. Baboota RK, Singh DP, Sarma SM, Kaur J, Sandhir R, Boparai RK, Kondepudi KK & Bishnoi M. Capsaicin induces "brite" phenotype in differentiating 3T3-L1 preadipocytes. PLoS ONE 2014 9 e103093. (doi:10.1371/journal.pone.0103093)
123. Galgani JE & Ravussin E. Effect of dihydrocapsiate on resting metabolic rate in humans. American Journal of Clinical Nutrition 2010 92 1089-1093. (doi:10.3945/ajcn.2010.30036)
124. Snitker S, Fujishima Y, Shen H, Ott S, Pi-Sunyer X, Furuhata Y, Sato H & Takahashi M. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. American Journal of Clinical Nutrition 2009 89 45-50. (doi:10.3945/ajcn.2008.26561)
125. Yoneshiro T, Aita S, Kawai Y, Iwanaga T & Saito M. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. American Journal of Clinical Nutrition 2012 95 845-850. (doi:10.3945/ajcn.111.018606)
126. Sugita J, Yoneshiro T, Hatano T, Aita S, Ikemoto T, Uchiwa H, Iwanaga T, Kameya T, Kawai Y & Saito M. Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men. British Journal of Nutrition 2013 110 733-738. (doi:10.1017/S0007114512005715)
127. Vrieze A, Schopman JE, Admiraal WM, Soeters MR, Nieuwdorp M, Verberne HJ & Holleman F. Fasting and postprandial activity of brown adipose tissue in healthy men. Journal of Nuclear Medicine 2012 53 1407-1410. (doi:10.2967/jnumed.111.100701)
128. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012 481 463-468. (doi:10.1038/nature10777)
129. Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE & Mantzoros CS. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 2012 61 1725-1738. (doi:10.1016/j.metabol.2012.09.002)
130. Kraemer RR, Shockett P, Webb ND, Shah U & Castracane VD. A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Hormone and Metabolic Research 2014 46 150-154. (doi:10.1055/s-0033-1355381)
131. Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J & Drevon CA. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS Journal 2014 281 739-749. (doi:10.1111/febs.12619)
132. Kurdiova T, Balaz M, Vician M, Maderova D, Vlcek M, Valkovic L, Srbecky M, Imrich R, Kyselovicova O, Belan V et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. Journal of Physiology 2014 592 1091-1107. (doi:10.1113/jphysiol.2013. 264655)
133. Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pollanen E, Makela KA, Kainulainen H, Hakkinen K, Nyman K et al. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? Journal of Physiology 2013 591 5393-5400. (doi:10.1113/jphysiol.2013.263707)
134. Hecksteden A, Wegmann M, Steffen A, Kraushaar J, Morsch A, Ruppenthal S, Kaestner L & Meyer T. Irisin and exercise training in humans - results from a randomized controlled training trial. BMC Medicine 2013 11 235. (doi:10.1186/1741-7015-11-235)
135. Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisloff U, Tjonna AE, Raastad T et al. Evidence against a beneficial effect of irisin in humans. PLoS ONE 2013 8 e73680. (doi:10.1371/journal.pone.0073680)
136. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA et al. FGF-21 as a novel metabolic regulator. Journal of Clinical Investigation 2005 115 1627-1635. (doi:10.1172/JCI23606)
137. Berglund ED, Li CY, Bina HA, Lynes SE, Michael MD, Shanafelt AB, Kharitonenkov A & Wasserman DH. Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 2009 150 4084-4093. (doi:10.1210/en.2009-0221)
138. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, Moller DE & Kharitonenkov A. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 2008 149 6018-6027. (doi:10.1210/en.2008-0816)
139. Lee P, Werner CD, Kebebew E & Celi FS. Functional thermogenic beige adipogenesis is inducible in human neck fat. International Journal of Obesity 2014 38 170-176. (doi:10.1038/ijo.2013.82)
140. Lee P, Brychta RJ, Linderman J, Smith S, Chen KY & Celi FS. Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis. Journal of Clinical Endocrinology and Metabolism 2013 98 E98-102. (doi:10.1210/jc.2012-3107)
141. Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, Kharitonenkov A, Flier JS, Maratos-Flier E et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes & Development 2012 26 271-281. (doi:10.1101/gad.177857.111)
142. Chen D, Zhao M, Harris SE & Mi Z. Signal transduction and biological functions of bone morphogenetic proteins. Frontiers in Bioscience 2004 9 349-358. (doi:10.2741/1090)
143. Elsen M, Raschke S, Tennagels N, Schwahn U, Jelenik T, Roden M, Romacho T & Eckel J. BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells. American Journal of Physiology. Cell Physiology 2014 306 C431-C440. (doi:10.1152/ajpcell. 00290.2013)
144. Sharma A, Huard C, Vernochet C, Ziemek D, Knowlton KM, Tyminski E, Paradis T, Zhang Y, Jones JE, von Schack D et al. Brown fat determination and development from muscle precursor cells by novel action of bone morphogenetic protein 6. PLoS ONE 2014 9 e92608. (doi:10.1371/journal.pone.0092608)
145. Inuzuka M, Tamura N, Yamada N, Katsuura G, Oyamada N, Taura D, Sonoyama T, Fukunaga Y, Ohinata K, Sone M et al. C-type natriuretic peptide as a new regulator of food intake and energy expenditure. Endocrinology 2010 151 3633-3642. (doi:10.1210/en.2010-0141)
146. Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessi-Fulgheri P, Zhang C, Takahashi N, Sarzani R & Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. Journal of Clinical Investigation 2012 122 1022-1036. (doi:10.1172/JCI59701)
147. 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 Metabolism 2009 9 203-209. (doi:10.1016/j.cmet.2008.12.014)
148. Kontani Y, Wang Y, Kimura K, Inokuma KI, Saito M, Suzuki-Miura T, Wang Z, Sato Y, Mori N & Yamashita H. UCP1 deficiency increases susceptibility to diet-induced obesity with age. Aging Cell 2005 4 147-155. (doi:10.1111/j.1474-9726.2005.00157.x)
149. Lowell BB, V SS, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP & Flier JS. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 1993 366 740-742. (doi:10.1038/366740a0)
150. Park JY, Lim JS, Park EY, Cho AR, Kim BI, Cheon GJ, Choi CW & Lim SM. The prevalence and characteristics of brown adipose tissue in an (18)F-FDG PET study of koreans. Nuclear Medicine and Molecular Imaging 2010 44 207-212. (doi:10.1007/s13139-010-0042-z)
151. Zhang Z, Cypess AM, Miao Q, Ye H, Liew CW, Zhang Q, Xue R, Zhang S, Zuo C, Xu Z et al. The prevalence and predictors of active brown adipose tissue in Chinese adults. European Journal of Endocrinology 2014 170 359-366. (doi:10.1530/EJE-13-0712)
152. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P & van Marken Lichtenbelt WD. Brown adipose tissue in morbidly obese subjects. PLoS ONE 2011 6 e17247. (doi:10.1371/journal.pone.0017247)
153. Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y & Saito M. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity 2011 19 13-16. (doi:10.1038/oby.2010.105)
154. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C et al. Brown adipose tissue activity controls triglyceride clearance. Nature Medicine 2011 17 200-205. (doi:10.1038/nm.2297)
155. Astrup A, Bulow J, Christensen NJ & Madsen J. Ephedrine-induced thermogenesis in man: no role for interscapular brown adipose tissue. Clinical Science 1984 66 179-186. (doi:10.1042/cs0660179)
156. Vosselman MJ, van der Lans AA, Brans B, Wierts R, van Baak MA, Schrauwen P & van Marken Lichtenbelt WD. Systemic β-adrenergic stimulation of thermogenesis is not accompanied by brown adipose tissue activity in humans. Diabetes 2012 61 3106-3113. (doi:10.2337/db12-0288)
157. Carey AL, Formosa MF, Van Every B, Bertovic D, Eikelis N, Lambert GW, Kalff V, Duffy SJ, Cherk MH & Kingwell BA. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia 2013 56 147-155. (doi:10.1007/s00125-012-2748-1)
158. Lee P, Day RO, Greenfield JR & Ho KK. Formoterol, a highly β2-selective agonist, increases energy expenditure and fat utilisation in men. International Journal of Obesity 2013 37 593-597. (doi:10.1038/ijo.2012.90)
159. Jang C, Jalapu S, Thuzar M, Law PW, Jeavons S, Barclay JL & Ho KK. Infrared thermography in the detection of brown adipose tissue in humans. Physiological Reports 2014 2 e12167. (doi:10.14814/phy2. 12167)
160. Lee P, Ho KK, Lee P, Greenfield JR, Ho KK & Greenfield JR. Hot fat in a cool man: infrared thermography and brown adipose tissue. Diabetes, Obesity & Metabolism 2011 13 92-93. (doi:10.1111/j.1463-1326.2010.01318.x)
161. Symonds ME, Henderson K, Elvidge L, Bosman C, Sharkey D, Perkins AC & Budge H. Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children. Journal of Pediatrics 2012 161 892-898. (doi:10.1016/j.jpeds.2012.04.056)
162. Chen YI, Cypess AM, Sass CA, Brownell AL, Jokivarsi KT, Kahn CR & Kwong KK. Anatomical and functional assessment of brown adipose tissue by magnetic resonance imaging. Obesity 2012 20 1519-1526. (doi:10.1038/oby.2012.22)
163. Reddy NL, Jones TA, Wayte SC, Adesanya O, Sankar S, Yeo YC, Tripathi G, McTernan PG, Randeva HS, Kumar S et al. Identification of brown adipose tissue using MR imaging in a human adult with histological and immunohistochemical confirmation. Journal of Clinical Endocrinology and Metabolism 2014 99 E117-E121. (doi:10.1210/jc.2013-2036)