REVIEW

Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity

  • Xuejiao Liu 1 ,
  • Christopher Cervantes 2 ,
  • Feng Liu , 1,2
Expand
  • 1. Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center of Central South University, The Second Xiangya Hospital, Central South University, Changsha 410011, China
  • 2. Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

Received date: 10 Nov 2016

Accepted date: 26 Jan 2017

Published date: 05 Jul 2017

Copyright

2017 The Author(s) 2017. This article is published with open access at Springerlink.com and journal.hep.com.cn

Abstract

Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing ‘metabolic panacea’.

Cite this article

Xuejiao Liu , Christopher Cervantes , Feng Liu . Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity[J]. Protein & Cell, 2017 , 8(6) : 446 -454 . DOI: 10.1007/s13238-017-0378-6

1
Aherne W, Hull D (1966) Brown adipose tissue and heat production in the newborn infant . J Pathol Bacteriol 91:223–234

DOI

2
Arch JR, Wilson S (1996) Beta 3-adrenoceptors and the regulation of metabolism in adipose tissues . Biochem Soc Trans 24:412–418

DOI

3
Barclay JL, Agada H, Jang C, Ward M, Wetzig N, Ho KK (2015) Effects of glucocorticoids on human brown adipocytes . J Endocrinol 224:139–147

DOI

4
Bonet ML, Oliver P, Palou A (2013) Pharmacological and nutritional agents promoting browning of white adipose tissue . Biochim Biophys Acta 1831:969–985

DOI

5
Bordicchia M, Liu D, Amri EZ (2012) Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes . J Clin Investig 122:1022–1036

DOI

6
Bostrom P, Wu J, Jedrychowski MP (2012) A PGC1-alphadependent myokine that drives brown-fat-like development of white fat and thermogenesis . Nature 481:463–468

DOI

7
Brestoff JR, Kim BS, Saenz SA (2015) Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity . Nature 519:242–246

DOI

8
Broeders EP, Nascimento EB, Havekes B (2015) The bile acid chenodeoxycholic acid increases human brown adipose tissue activity . Cell Metab 22:418–426

DOI

9
Cannon B, Nedergaard J (2011) Nonshivering thermogenesis and its adequate measurement in metabolic studies . J Exper Biol 214:242–253

DOI

10
Carriere A, Jeanson Y, Berger-Muller S (2014) Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure . Diabetes 63:3253–3265

DOI

11
Chen YC, Cypess AM, Chen YC (2013) Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging . J Nucl Med 54:1584–1587

DOI

12
Crisan M, Casteilla L, Lehr L (2008) A reservoir of brown adipocyte progenitors in human skeletal muscle . Stem Cells 26:2425–2433

DOI

13
Cypess AM, Lehman S, Williams G (2009) Identification and importance of brown adipose tissue in adult humans . N Engl J Med 360:1509–1517

DOI

14
Cypess AM, Chen YC, Sze C (2012) Cold but not sympathomimetics activates human brown adipose tissue in vivo . Proc Natl Acad Sci USA 109:10001–10005

DOI

15
Cypess AM, White AP, Vernochet C (2013) Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat . Nat Med 19:635–639

DOI

16
Daniel Ricquier J-CK (1976) Mitochondrial protein alterations in active brown fat: a sodium dodecyl sulfate-polyacrylamide gel electrophoretic study . Biochem Biophys Res Commun 73:577–583

DOI

17
DiGirolamo M, Newby FD, Lovejoy J (1992) Lactate production in adipose tissue: a regulated function with extra-adipose implications . FASEB J 6:2405–2412

18
Eckel RH, Alberti KG, Grundy SM, Zimmet PZ (2010) The metabolic syndrome . Lancet 375:181–183

DOI

19
Eger W (1954) The significance of fatty tissue in obesity. I. On the histology, physiology and pathology of the white and brown fatty tissue . Die Med 20:701–704

20
Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality . Cell Metab 9:203–209

DOI

21
Gifford A, Towse TF, Walker RC, Avison MJ, Welch EB (2015) Human brown adipose tissue depots automatically segmented by positron emission tomography/computed tomography and registered magnetic resonance images . J Vis Exp 96:e52415

DOI

22
Grosfeld A, Zilberfarb V, Turban S, Andre J, Guerre-Millo M, Issad T (2002) Hypoxia increases leptin expression in human PAZ6 adipose cells . Diabetologia 45:527–530

DOI

23
Guller I, McNaughton S, Crowley T (2015) Comparative analysis of microRNA expression in mouse and human brown adipose tissue . BMC Genom 16:820

DOI

24
Hall KD, Sacks G, Chandramohan D (2011) Quantification of the effect of energy imbalance on bodyweight . Lancet 378:826–837

DOI

25
Hanssen MJ, Wierts R, Hoeks J (2015) Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance . Diabetologia 58:586–595

DOI

26
Hatai S (1902) On the presence in human embryos of an interscapular gland corresponding to the so-called hibernating gland of lower mammals . Anat Anz 21:369–373

27
Heaton JM (1972) The distribution of brown adipose tissue in the human . J Anat 112:35–39

28
Himms-Hagen J (1979) Obesity may be due to a malfunctioning of brown fat . Can Med Assoc J 121:1361–1364

29
Hirschberg V, Fromme T, Klingenspor M (2011) Test systems to study the structure and function of uncoupling protein 1: a critical overview . Front Endocrinol 2:63

DOI

30
Hondares E, Gallego-Escuredo JM, Flachs P (2014) Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue . Metabolism 63:312–317

DOI

31
Hughes DA, Jastroch M, Stoneking M, Klingenspor M (2009) Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis . BMC Evol Biol 9:4

DOI

32
Huttunen P, Hirvonen J, Kinnula V (1981) The occurrence of brown adipose tissue in outdoor workers . Eur J Appl Physiol 46:339–345

DOI

33
Ishibashi J, Seale P (2010) Medicine. Beige can be slimming . Science 328:1113–1114

DOI

34
Jespersen NZ, Larsen TJ, Peijs L (2013) A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans . Cell Metab 17:798–805

DOI

35
Jimenez-Preitner M, Berney X, Uldry M (2011) Plac8 is an inducer of C/EBPbeta required for brown fat differentiation, thermoregulation, and control of body weight . Cell Metab 14:658–670

DOI

36
Jockers R, Issad T, Zilberfarb V, de Coppet P, Marullo S, Strosberg AD (1998) Desensitization of the beta-adrenergic response in human brown adipocytes . Endocrinology 139:2676–2684

DOI

37
Kajimura S, Seale P, Kubota K (2009) Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex . Nature 460:1154–1158

DOI

38
Kurdiova T, Balaz M, Vician M (2014) 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 . J Physiol 592:1091–1107

DOI

39
Lee P, Brychta RJ, Linderman J, Smith S, Chen KY, Celi FS (2013) Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis . J Clin Endocrinol Metab 98:E98–E102

DOI

40
Lee P, Linderman JD, Smith S (2014) Irisin and FGF21 are coldinduced endocrine activators of brown fat function in humans . Cell Metab 19:302–309

DOI

41
Lee P, Bova R, Schofield L (2016) Brown adipose tissue exhibits a glucose-responsive thermogenic biorhythm in humans . Cell Metab 23:602–609

DOI

42
Liu PS, Lin YW, Lee B, McCrady-Spitzer SK, Levine JA, Wei LN (2014) Reducing RIP140 expression in macrophage alters ATM infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance . Diabetes 63:4021–4031

DOI

43
Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis . Nature 404:652–660

44
Moro C, Pillard F, de Glisezinski I (2008) Exercise-induced lipid mobilization in subcutaneous adipose tissue is mainly related to natriuretic peptides in overweight men . Am J Physiol Endocrinol Metab 295:E505–E513

DOI

45
Nedergaard J, Bengtsson T, Cannon B (2007) Unexpected evidence for active brown adipose tissue in adult humans . Am J Physiol Endocrinol Metab 293:E444–E452

DOI

46
Nguyen KD, Qiu Y, Cui X (2011) Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis . Nature 480:104–108

DOI

47
Nicholls DG, Locke RM (1984) Thermogenic mechanisms in brown fat . Physiol Rev 64:1–64

48
Oberkofler H, Esterbauer H, Linnemayr V, Strosberg AD, Krempler F, Patsch W (2002) Peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 recruitment regulates PPAR subtype specificity . J Biol Chem 277:16750–16757

DOI

49
Orava J, Nuutila P, Lidell ME (2011) Different metabolic responses of human brown adipose tissue to activation by cold and insulin . Cell Metab 14:272–279

DOI

50
Qiu Y, Nguyen KD, Odegaard JI (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat . Cell 157:1292–1308

DOI

51
Ramage LE, Akyol M, Fletcher AM (2016) Glucocorticoids acutely increase brown adipose tissue activity in humans, revealing species-specific differences in UCP-1 regulation . Cell Metab 24:130–141

DOI

52
Rice SP, Zhang L, Grennan-Jones F (2010) Dehydroepiandrosterone (DHEA) treatment in vitro inhibits adipogenesis in human omental but not subcutaneous adipose tissue . Mol Cell Endocrinol 320:51–57

DOI

53
Saito M, Okamatsu-Ogura Y, Matsushita M (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity . Diabetes 58:1526–1531

DOI

54
Seale P, Bjork B, Yang W (2008) PRDM16 controls a brown fat/skeletal muscle switch . Nature 454:961–967

DOI

55
Shimizu Y, Nikami H, Saito M (1991) Sympathetic activation of glucose utilization in brown adipose tissue in rats . J Biochem 110:688–692

DOI

56
Smith RE, Roberts JC (1964) Thermogenesis of brown adipose tissue in cold-acclimated rats . Am J Physiol 206:143–148

57
Speakman JR, Selman C (2003) Physical activity and resting metabolic rate . Proc Nutr Soc 62:621–634

DOI

58
Strobel A, Siquier K, Zilberfarb V, Strosberg AD, Issad T (1999) Effect of thiazolidinediones on expression of UCP2 and adipocyte markers in human PAZ6 adipocytes . Diabetologia 42:527–533

DOI

59
Svensson PA, Jernas M, Sjoholm K (2011) Gene expression in human brown adipose tissue . Int J Mol Med 27:227–232

DOI

60
Trayhurn P, Alomar SY (2015) Oxygen deprivation and the cellular response to hypoxia in adipocytes: perspectives on white and brown adipose tissues in obesity . Front Endocrinol 6:19

DOI

61
van Baak MA, Hul GB, Toubro S (2002) Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy expenditure in obese men . Clin Pharmacol Ther 71:272–279

DOI

62
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM (2009) Cold-activated brown adipose tissue in healthy men . N Engl J Med 360:1500–1508

DOI

63
Vijgen GH, Bouvy ND, Leenen L (2013) Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity . PLoS ONE 8:e77221

DOI

64
Virtanen KA, Lidell ME, Orava J (2009) Functional brown adipose tissue in healthy adults . N Engl J Med 360:1518–1525

DOI

65
World Health Organization Fact Sheets: Obesity and Overweight (2016) (article online).

66
Wu D, Molofsky AB, Liang HE (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis . Science 332:243–247

DOI

67
Wu J, Bostrom P, Sparks LM (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human . Cell 150:366–376

DOI

68
Yoneshiro T, Ogawa T, Okamoto N (2005) Impact of UCP1 and beta3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans . Int J Obes 2013 (37):993–998

69
Zilberfarb V, Pietri-Rouxel F, Jockers R (1997) Human immortalized brown adipocytes express functional beta3-adrenoceptor coupled to lipolysis . J Cell Sci 110(Pt 7):801–807

70
Zilberfarb V, Siquier K, Strosberg AD, Issad T (2001) Effect of dexamethasone on adipocyte differentiation markers and tumour necrosis factor-alpha expression in human PAZ6 cells . Diabetologia 44:377–386

DOI

Outlines

/