INDUCTION OF BROWN ADIPOSE TISSUE: A REVIEW
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i5.22646Keywords:
Brown adipose tissue, White adipose tissue, uncoupling protein-1, Irisin hormone, Thermogenesis, Nil, PRDM16, NilAbstract
Objective: Obesity is the major problem which may lead to many other health ailments such as atherosclerosis, stroke, and depression. Both the cause as well as the treatment lies in the adipose tissue. The two main adipocytes, white adipose tissue (WAT) and brown adipose tissue (BAT) are responsible for the accumulation of fat and transformation of fat into heat, respectively. This review discusses the induction of BAT and browning of WAT by different pathways and activators to decrease the rate of obesity.
Methods: Understanding the regulators, activators and secreted proteins which induce browning of WAT to BAT, as the BAT engage in thermogenesis process and transform fat into heat rather than storing it (WAT). Some of the core regulators are peroxisome proliferator-activated receptor-γ, PRDM16, PGC-1α.
Results: A basic study explained about the origin of BAT and its functions, the function of hormones in BAT growth and its regulations. These studies provided the platform to understand about the mechanism of regulators, activators and secreted proteins which help in treating obesity and its related disorders by inducing the amount of BAT.
Conclusion: The major health ailments caused by obesity can be reduced by increasing the activity of BAT and transforming WAT into BAT. A challenging way to treat these ailments is by regulating the activators and hormones responsible for the induction of BAT, so it transforms the excess fat into heat and avoiding the accumulation of fat. By understanding the role of regulators in the adipose tissue can provide various methods to reduce the chance of obesity and enhance efficient treatment in both children and adults.
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References
Seale P, Lazar MA. Brown fat in humans: Turning up the heat on obesity. Diabetes 2009;58:1482-4.
Enerback S. The origins of brown adipose tissue. N Engl J Med 2009;360:2021-3.
Cypess AM, Kahn CR. The role and importance of brown adipose tissue in energy homeostasis. Curr Opin Pediatr 2010;22:478-84.
Lo KA, Sun L. Turning WAT into BAT: A review on regulators controlling the browning of white adipocytes. Biosci Rep 2013;33:e00065.
Carter BW, Schucany WG. Brown adipose tissue in a newborn. Proc (Bayl Univ Med Cent) 2008;21:328.
Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes 2014;63:514-25.
Sidossis L, Kajimura S. Brown and beige fat in humans: Thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest 2015;125:478-86.
Kim SH, Plutzky J. Brown fat and browning for the treatment of obesity and related metabolic disorders. Diabetes Metab J 2016;40:12-21.
Jung UJ, Choi MS. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014;15:6184-223.
Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-56.
Harms M, Seale P. Brown and beige fat: Development, function and therapeutic potential. Nat Med 2013;19:1252-63.
Blaza S. Brown adipose tissue in man: A review. J R Soc Med 1983;76:213-6.
Ricquier D, Bouillaud F. Mitochondrial uncoupling proteins: From mitochondria to the regulation of energy balance. J Physiol 2000;529:3- 10.
Inokuma K, Ogura-Okamatsu Y, Toda C, Kimura K, Yamashita H, Saito M, et al. Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization in brown adipose tissue. Diabetes 2005;54:1385-91.
Cannon B, Nedergaard JA. Brown adipose tissue: Function and physiological significance. Physiol Rev 2004;84:277-359.
Kajimura S, Spiegelman BM, Seale P. Brown and beige fat: Physiological roles beyond heat generation. Cell Metab 2015;22:546- 59.
Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM 2,4-dinitrophenol (DNP): A weight loss agent with significant acute toxicity and risk of death. J Med Toxicol 2011;7:205-12.
Brondani LA, Assmann TS, Duarte GC, Gross JL, Canani LH, Crispim D, et al. The role of the uncoupling protein 1 (UCP1) on the development of obesity and Type 2 diabetes mellitus. Arq Bras Endocrinol Metabol 2012;56:215-25.
Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD. Mitochondrial uncoupling and lifespan. Mech Ageing Dev 2010;131:463-72.
Gurnell M. PPARγ and metabolism: Insights from the study of human genetic variants. Clin Endocrinol 2003;59:267-77.
Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 2014;19:302-9.
Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. PPARγ is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 1999;4:611-7.
Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-deoxy-Δ12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 1995;83:803-12.
Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell 1995;83:813-9.
Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proc Natl Acad Sci 1997;94:4318-23.
Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. Cell 1998;93:229-40.
Imai T, Takakuwa R, Marchand S, Dentz E, Bornert JM, Messaddeq N, et al. Peroxisome proliferator-activated receptor γ is required in mature white and brown adipocytes for their survival in the mouse. Proc Natl Acad Sci U S A 2004;101:4543-7.
Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab 2012;15:395-404.
Chartoumpekis DV, Habeos IG, Ziros PG, Psyrogiannis AI, Kyriazopoulou VE, Papavassiliou AG, et al. Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21. Mol Med 2011;17:736-40.
Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, et al. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem 2011;286:12983-90.
Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 2008;149:6018-27.
Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 2012;26:271-81.
Sengenès C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J. Natriuretic peptides: A new lipolytic pathway in human adipocytes. FASEB J 2000;14:1345-51.
Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessì-Fulgheri P, Zhang C, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest 2012;122:1022-36.
Zamani N, Brown CW. Emerging roles for the transforming growth factor-β superfamily in regulating adiposity and energy expenditure. Endocr Rev 2010;32:387-403.
Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 2008;454:1000-4.
Qian SW, Tang Y, Li X, Liu Y, Zhang YY, Huang HY, et al. BMP4- mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proc Natl Acad Sci U S A 2013;110:E798-807.
Kiefer FW, Vernochet C, O’Brien P, Spoerl S, Brown JD, Nallamshetty S, et al. Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue. Nat Med 2012;18:918-25.
Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008;454:961-7.
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-β transcriptional complex. Nature 2009;460:1154-8.
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.
Kajimura S, Seale P, Tomaru T, Erdjument-Bromage H, Cooper MP, Ruas JL, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev 2008;22:1397-409.
Waldén TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J. Recruited vs. Nonrecruited molecular signatures of brown,brite,†and white adipose tissues. Am J Physiol Endocrinol Metab 2012;302:E19- 31.
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM, et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998;92:829-39.
Pardo R, Enguix N, Lasheras J, Feliu JE, Kralli A, Villena JA. Rosiglitazone-induced mitochondrial biogenesis in white adipose tissue is independent of peroxisome proliferator-activated receptor γ coactivator-1α. PLoS One 2011;6:e26989.
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-[agr]-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012;481:463-8.
Scimè A, Grenier G, Huh MS, Gillespie MA, Bevilacqua L, Harper ME, et al. Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1α. Cell Metab 2005;2:283-95.
Morrison SF, Madden CJ, Tupone D. Central control of brown adipose tissue thermogenesis. Front Endocrinol (Lausanne) 2012;3.
Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, et al. Eosinophils and Type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 2014;157:1292-308.
Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 2014;157:1279-91.
Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature 2008;454:463-9.
Knudsen JG, Murholm M, Carey AL, Biensø RS, Basse AL, Allen TL, et al. Role of IL-6 in exercise training- and cold-induced UCP1 expression in subcutaneous white adipose tissue. PLoS One 2014;9:e84910.
Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med 2011;17:200-5.
Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 2013;123:215-23.
Rajakumari S, Wu J, Ishibashi J, Lim HW, Giang AH, Won KJ, et al. EBF2 determines and maintains brown adipocyte identity. Cell Metab 2013;17:562-74.
Sarkar SJ, Dioundi D, Gupta M. Endophytic Pestalotiopsis species from Andaman Islands: A potential pancreatic lipase inhibitor. Asian J Pharm Clin Res 2017;10:82-3.
Bollapragada M, Shantaram M, Sunil Kumar R. Obesity: Development, epidemiology, factors affecting, quantity, health hazards, management and natural treatment-a review. Int J Pharm Pharm Sci 2017;9:12-26.
Mohamed HO, Asker ME, Amin RA, Eissa RA. Anti-obesity effect of resveratrol in rats on high fat diet through regulation of gene expression of visceral white adipose tissue. Int J Pharm Pharm Sci 2016;8:378-84.
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