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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2015, Vol. 9 Issue (2) : 162-172     DOI: 10.1007/s11684-015-0382-2
REVIEW |
Brown and beige fat: the metabolic function, induction, and therapeutic potential
Shuwen Qian,Haiyan Huang,Qiqun Tang()
Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China
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Abstract  

Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.

Keywords brown adipocyte      beige adipocyte      metabolism      obesity     
Corresponding Authors: Qiqun Tang   
Online First Date: 08 January 2015    Issue Date: 22 May 2015
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-015-0382-2     OR     http://academic.hep.com.cn/fmd/EN/Y2015/V9/I2/162
Fig.1  Origin and molecular signature of adipocytes: classical brown adipocytes derive from myf5+ precursors. White and beige adipocytes derive from myf5- precursors, but may come from two distinct population of precursors. Some molecular markers express in different kind of adipocytes or fat depots.
Fig.2  Vasculature contributes to adipose expansion in variety of ways. Angiogenic vessels supply nutrients and oxygen in the blood to adipocytes. Angiogenic vessels transport mesenchymal stem cells (MSC) from bone marrow, or provide stem cells derived from themselves. Adipocytes produce various growth factors and cytokines that communicate with endothelial cells in a paracrine fashion to promote their growth.
1 Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384(9945): 766–781
doi: 10.1016/S0140-6736(14)60460-8 pmid: 24880830
2 Bornfeldt KE, Tabas I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab 2011; 14(5): 575–585
doi: 10.1016/j.cmet.2011.07.015 pmid: 22055501
3 Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott M, Meigs J, Mozaffarian D, Nichol G, O’Donnell C, Roger V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T, Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009; 119(3): 480–486
doi: 10.1161/CIRCULATIONAHA.108.191259 pmid: 19171871
4 Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell 2007; 131(2): 242–256
doi: 10.1016/j.cell.2007.10.004 pmid: 17956727
5 Virtanen KA, Nuutila P. Brown adipose tissue in humans. Curr Opin Lipidol 2011; 22(1): 49–54
doi: 10.1097/MOL.0b013e3283425243 pmid: 21157334
6 Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444(7121): 847–853
doi: 10.1038/nature05483 pmid: 17167472
7 Cannon B, Houstek J, Nedergaard J. Brown adipose tissue. More than an effector of thermogenesis? Ann N Y Acad Sci 1998; 856(1 MOLECULAR MEC): 171–187
doi: 10.1111/j.1749-6632.1998.tb08325.x pmid: 9917877
8 Villarroya J, Cereijo R, Villarroya F. An endocrine role for brown adipose tissue? Am J Physiol Endocrinol Metab 2013; 305(5): E567–E572
doi: 10.1152/ajpendo.00250.2013 pmid: 23839524
9 Young P, Arch JR, Ashwell M. Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Lett 1984; 167(1): 10–14
doi: 10.1016/0014-5793(84)80822-4 pmid: 6698197
10 Loncar D, Afzelius BA, Cannon B. Epididymal white adipose tissue after cold stress in rats. I. Nonmitochondrial changes. J Ultrastruct Mol Struct Res 1988; 101(2–3): 109–122
doi: 10.1016/0889-1605(88)90001-8 pmid: 3268608
11 Loncar D, Afzelius BA, Cannon B. Epididymal white adipose tissue after cold stress in rats. II. Mitochondrial changes. J Ultrastruct Mol Struct Res 1988; 101(2–3): 199–209
doi: 10.1016/0889-1605(88)90010-9 pmid: 3151905
12 Loncar D, Bedrica L, Mayer J, Cannon B, Nedergaard J, Afzelius BA, Svajger A. The effect of intermittent cold treatment on the adipose tissue of the cat. Apparent transformation from white to brown adipose tissue. J Ultrastruct Mol Struct Res 1986; 97(1–3): 119–129
doi: 10.1016/S0889-1605(86)80012-X pmid: 3453365
13 Almind K, Manieri M, Sivitz WI, Cinti S, Kahn CR. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice. Proc Natl Acad Sci USA 2007; 104(7): 2366–2371
doi: 10.1073/pnas.0610416104 pmid: 17283342
14 Xue B, Rim JS, Hogan JC, Coulter AA, Koza RA, Kozak LP. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J Lipid Res 2007; 48(1): 41–51
doi: 10.1194/jlr.M600287-JLR200 pmid: 17041251
15 Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. 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): 412–420
doi: 10.1172/JCI3155 pmid: 9664083
16 Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Pénicaud L, Casteilla L. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 1992; 103(Pt 4): 931–942
pmid: 1362571
17 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. Am J Physiol Cell Physiol 2000; 279(3): C670–C681
pmid: 10942717
18 Picó C, Bonet ML, Palou A. Stimulation of uncoupling protein synthesis in white adipose tissue of mice treated with the beta 3-adrenergic agonist CGP-12177. Cell Mol Life Sci 1998; 54(2): 191–195
doi: 10.1007/s000180050142 pmid: 9539963
19 Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2007; 293(2): E444–E452
doi: 10.1152/ajpendo.00691.2006 pmid: 17473055
20 Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009; 360(15): 1509–1517
doi: 10.1056/NEJMoa0810780 pmid: 19357406
21 Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009; 58(7): 1526–1531
doi: 10.2337/db09-0530 pmid: 19401428
22 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. N Engl J Med 2009; 360(15): 1500–1508
doi: 10.1056/NEJMoa0808718 pmid: 19357405
23 Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerb?ck S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med 2009; 360(15): 1518–1525
doi: 10.1056/NEJMoa0808949 pmid: 19357407
24 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 J 2009; 23(9): 3113–3120
doi: 10.1096/fj.09-133546 pmid: 19417078
25 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-beta transcriptional complex. Nature 2009; 460(7259): 1154–1158
doi: 10.1038/nature08262 pmid: 19641492
26 Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 2007; 104(11): 4401–4406
doi: 10.1073/pnas.0610615104 pmid: 17360536
27 Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008; 454(7207): 961–967
doi: 10.1038/nature07182 pmid: 18719582
28 Wu J, Bostr?m P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerb?ck S, Schrauwen P, Spiegelman BM. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150(2): 366–376
doi: 10.1016/j.cell.2012.05.016 pmid: 22796012
29 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(1): E19–E31
doi: 10.1152/ajpendo.00249.2011 pmid: 21828341
30 Sharp LZ, Shinoda K, Ohno H, Scheel DW, Tomoda E, Ruiz L, Hu H, Wang L, Pavlova Z, Gilsanz V, Kajimura S. Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS ONE 2012; 7(11): e49452
doi: 10.1371/journal.pone.0049452 pmid: 23166672
31 Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P, Virtanen KA, Beuschlein F, Persson A, Borga M, Enerb?ck S. Evidence for two types of brown adipose tissue in humans. Nat Med 2013; 19(5): 631–634
doi: 10.1038/nm.3017 pmid: 23603813
32 Lidell ME, Betz MJ, Enerb?ck S. Two types of brown adipose tissue in humans. Adipocyte 2014; 3(1): 63–66
doi: 10.4161/adip.26896 pmid: 24575372
33 Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, Huang TL, Roberts-Toler C, Weiner LS, Sze C, Chacko AT, Deschamps LN, Herder LM, Truchan N, Glasgow AL, Holman AR, Gavrila A, Hasselgren PO, Mori MA, Molla M, Tseng YH. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med 2013; 19(5): 635–639
doi: 10.1038/nm.3112 pmid: 23603815
34 Jespersen NZ, Larsen TJ, Peijs L, Daugaard S, Hom?e P, Loft A, de Jong J, Mathur N, Cannon B, Nedergaard J, Pedersen BK, M?ller K, Scheele C. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab 2013; 17(5): 798–805
doi: 10.1016/j.cmet.2013.04.011 pmid: 23663743
35 Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84(1): 277–359
doi: 10.1152/physrev.00015.2003 pmid: 14715917
36 Foster DO, Frydman ML. Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: the dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis. Can J Physiol Pharmacol 1979; 57(3): 257–270
doi: 10.1139/y79-039 pmid: 445227
37 Rothwell NJ, Stock MJ. Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci (Lond)1983; 64(1): 19–23
pmid: 6337007
38 Ghorbani M, Claus TH, 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): 121–131
doi: 10.1016/S0006-2952(97)00162-7 pmid: 9296358
39 Lowell BB, S-Susulic V, 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(6457): 740–742
doi: 10.1038/366740a0 pmid: 8264795
40 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. J Clin Endocrinol Metab 2011; 96(1): 192–199
doi: 10.1210/jc.2010-0989 pmid: 20943785
41 Nikami H, Shimizu Y, Endoh D, Yano H, Saito M. Cold exposure increases glucose utilization and glucose transporter expression in brown adipose tissue. Biochem Biophys Res Commun 1992; 185(3): 1078–1082
doi: 10.1016/0006-291X(92)91736-A pmid: 1378263
42 Dallner OS, Chernogubova E, Brolinson KA, Bengtsson T. Beta3-adrenergic receptors stimulate glucose uptake in brown adipocytes by two mechanisms independently of glucose transporter 4 translocation. Endocrinology 2006; 147(12): 5730–5739
doi: 10.1210/en.2006-0242 pmid: 16959848
43 Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 2013; 123(1): 215–223
doi: 10.1172/JCI62308 pmid: 23221344
44 Crandall DL, Hausman GJ, Kral JG. A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives. Microcirculation 1997; 4(2): 211–232
doi: 10.3109/10739689709146786 pmid: 9219215
45 Jansson PA. Endothelial dysfunction in insulin resistance and type 2 diabetes. J Intern Med 2007; 262(2): 173–183
doi: 10.1111/j.1365-2796.2007.01830.x pmid: 17645585
46 Sierra-Honigmann MR, Nath AK, Murakami C, García-Carde?a G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR. Biological action of leptin as an angiogenic factor. Science 1998; 281(5383): 1683–1686
doi: 10.1126/science.281.5383.1683 pmid: 9733517
47 Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest 2007; 117(9): 2362–2368
doi: 10.1172/JCI32239 pmid: 17786229
48 Voros G, Maquoi E, Demeulemeester D, Clerx N, Collen D, Lijnen HR. Modulation of angiogenesis during adipose tissue development in murine models of obesity. Endocrinology 2005; 146(10): 4545–4554
doi: 10.1210/en.2005-0532 pmid: 16020476
49 Wang Y, Lam JB, Lam KS, Liu J, Lam MC, Hoo RL, Wu D, Cooper GJ, Xu A. Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res 2006; 66(23): 11462–11470
doi: 10.1158/0008-5472.CAN-06-1969 pmid: 17145894
50 Br?kenhielm E, Veitonm?ki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, Funahashi T, Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA 2004; 101(8): 2476–2481
doi: 10.1073/pnas.0308671100 pmid: 14983034
51 Cao R, Brakenhielm E, Wahlestedt C, Thyberg J, Cao Y. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci USA 2001; 98(11): 6390–6395
doi: 10.1073/pnas.101564798 pmid: 11344271
52 Hausman GJ, Richardson RL. Adipose tissue angiogenesis. J Anim Sci 2004; 82(3): 925–934
pmid: 15032451
53 Zhang QX, Magovern CJ, Mack CA, Budenbender KT, Ko W, Rosengart TK. Vascular endothelial growth factor is the major angiogenic factor in omentum: mechanism of the omentum-mediated angiogenesis. J Surg Res 1997; 67(2): 147–154
doi: 10.1006/jsre.1996.4983 pmid: 9073561
54 Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999; 13(1): 9–22
pmid: 9872925
55 Elias I, Franckhauser S, Ferré T, Vilà L, Tafuro S, Mu?oz S, Roca C, Ramos D, Pujol A, Riu E, Ruberte J, Bosch F. Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance. Diabetes 2012; 61(7): 1801–1813
doi: 10.2337/db11-0832 pmid: 22522611
56 Sung HK, Doh KO, Son JE, Park JG, Bae Y, Choi S, Nelson SM, Cowling R, Nagy K, Michael IP, Koh GY, Adamson SL, Pawson T, Nagy A. Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab 2013; 17(1): 61–72
doi: 10.1016/j.cmet.2012.12.010 pmid: 23312284
57 Sun K, Wernstedt Asterholm I, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, Brekken RA, Scherer PE. Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc Natl Acad Sci USA 2012; 109(15): 5874–5879
doi: 10.1073/pnas.1200447109 pmid: 22451920
58 Shimizu I, Aprahamian T, Kikuchi R, Shimizu A, Papanicolaou KN, MacLauchlan S, Maruyama S, Walsh K. Vascular rarefaction mediates whitening of brown fat in obesity. J Clin Invest 2014; 124(5): 2099–2112
doi: 10.1172/JCI71643 pmid: 24713652
59 Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S, Feldmann HM, Liang Z, Zhu Z, Nedergaard J, Cannon B, Cao Y. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab 2009; 9(1): 99–109
doi: 10.1016/j.cmet.2008.11.009 pmid: 19117550
60 Crossno JT Jr, Majka SM, Grazia T, Gill RG, Klemm DJ. Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J Clin Invest 2006; 116(12): 3220–3228
doi: 10.1172/JCI28510 pmid: 17143331
61 Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Péault B. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008; 3(3): 301–313
doi: 10.1016/j.stem.2008.07.003 pmid: 18786417
62 Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, Johnstone BH, March KL. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res 2008; 102(1): 77–85
doi: 10.1161/CIRCRESAHA.107.159475 pmid: 17967785
63 Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, Smorlesi A, Perugini J, De Matteis R, Sbarbati A, Corvera S, Cinti S. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab 2012; 15(2): 222–229
doi: 10.1016/j.cmet.2012.01.008 pmid: 22326223
64 Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM. White fat progenitor cells reside in the adipose vasculature. Science 2008; 322(5901): 583–586
doi: 10.1126/science.1156232 pmid: 18801968
65 da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells. Stem Cells 2008; 26(9): 2287–2299
doi: 10.1634/stemcells.2007-1122 pmid: 18566331
66 Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 2013; 19(10): 1338–1344
doi: 10.1038/nm.3324 pmid: 23995282
67 Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, Mukundan L, Brombacher F, Locksley RM, Chawla A. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 2011; 480(7375): 104–108
doi: 10.1038/nature10653 pmid: 22101429
68 Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, Palmiter RD, Chawla A. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 2014; 157(6): 1292–1308
doi: 10.1016/j.cell.2014.03.066 pmid: 24906148
69 Nicholls DG. The physiological regulation of uncoupling proteins. Biochim Biophys Acta 2006; 1757(5–6): 459–466
doi: 10.1016/j.bbabio.2006.02.005 pmid: 16725104
70 Fedorenko A, Lishko PV, Kirichok Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 2012; 151(2): 400–413
doi: 10.1016/j.cell.2012.09.010 pmid: 23063128
71 Robidoux J, Cao W, Quan H, Daniel KW, Moukdar F, Bai X, Floering LM, Collins S. Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes. Mol Cell Biol 2005; 25(13): 5466–5479
doi: 10.1128/MCB.25.13.5466-5479.2005 pmid: 15964803
72 Bonet ML, Oliver P, Palou A. Pharmacological and nutritional agents promoting browning of white adipose tissue. Biochim Biophys Acta 2013; 1831(5): 969–985
doi: 10.1016/j.bbalip.2012.12.002 pmid: 23246573
73 Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol 2004; 24(7): 3057–3067
doi: 10.1128/MCB.24.7.3057-3067.2004 pmid: 15024092
74 Bukowiecki L, Collet AJ, Follea N, Guay G, Jahjah L. Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia. Am J Physiol 1982; 242(6): E353–E359
pmid: 6953766
75 Desautels M, Dulos RA, Mozaffari B. Selective loss of uncoupling protein from mitochondria of surgically denervated brown adipose tissue of cold-acclimated mice. Biochem Cell Biol 1986; 64(11): 1125–1134
doi: 10.1139/o86-148 pmid: 3828106
76 Murano I, Barbatelli G, Giordano A, Cinti S. Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ. J Anat 2009; 214(1): 171–178
doi: 10.1111/j.1469-7580.2008.01001.x pmid: 19018882
77 Jimenez M, Barbatelli G, Allevi R, Cinti S, Seydoux J, Giacobino JP, Muzzin P, Preitner F. Beta 3-adrenoceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white fat. Eur J Biochem 2003; 270(4): 699–705
doi: 10.1046/j.1432-1033.2003.03422.x pmid: 12581209
78 Mori M, Nakagami H, Rodriguez-Araujo G, Nimura K, Kaneda Y. Essential role for miR-196a in brown adipogenesis of white fat progenitor cells. PLoS Biol 2012; 10(4): e1001314
doi: 10.1371/journal.pbio.1001314 pmid: 22545021
79 Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS. miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 2009; 24(5): 816–825
doi: 10.1359/jbmr.081230 pmid: 19063684
80 Vegiopoulos A, Müller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A, Berriel Diaz M, Rozman J, Hrabe de Angelis M, Nüsing RM, Meyer CW, Wahli W, Klingenspor M, Herzig S. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 2010; 328(5982): 1158–1161
doi: 10.1126/science.1186034 pmid: 20448152
81 Madsen L, Pedersen LM, Lillefosse HH, Fjaere E, Bronstad I, Hao Q, Petersen RK, Hallenborg P, Ma T, De Matteis R, Araujo P, Mercader J, Bonet ML, Hansen JB, Cannon B, Nedergaard J, Wang J, Cinti S, Voshol P, D?skeland SO, Kristiansen K. UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity. PLoS ONE 2010; 5(6): e11391
doi: 10.1371/journal.pone.0011391 pmid: 20613988
82 Kim JK, Kim HJ, Park SY, Cederberg A, Westergren R, Nilsson D, Higashimori T, Cho YR, Liu ZX, Dong J, Cline GW, Enerback S, Shulman GI. Adipocyte-specific overexpression of FOXC2 prevents diet-induced increases in intramuscular fatty acyl CoA and insulin resistance. Diabetes 2005; 54(6): 1657–1663
doi: 10.2337/diabetes.54.6.1657 pmid: 15919786
83 Xue Y, Cao R, Nilsson D, Chen S, Westergren R, Hedlund EM, Martijn C, Rondahl L, Krauli P, Walum E, Enerb?ck S, Cao Y. FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue. Proc Natl Acad Sci USA 2008; 105(29): 10167–10172
doi: 10.1073/pnas.0802486105 pmid: 18621714
84 Lidell ME, Seifert EL, Westergren R, Heglind M, Gowing A, Sukonina V, Arani Z, Itkonen P, Wallin S, Westberg F, Fernandez-Rodriguez J, Laakso M, Nilsson T, Peng XR, Harper ME, Enerb?ck S. The adipocyte-expressed forkhead transcription factor Foxc2 regulates metabolism through altered mitochondrial function. Diabetes 2011; 60(2): 427–435
doi: 10.2337/db10-0409 pmid: 21270254
85 Cederberg A, Gr?nning LM, Ahrén B, Taskén K, Carlsson P, Enerb?ck S. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 2001; 106(5): 563–573
doi: 10.1016/S0092-8674(01)00474-3 pmid: 11551504
86 Dahle MK, Gr?nning LM, Cederberg A, Blomhoff HK, Miura N, Enerb?ck S, Taskén KA, Taskén K. Mechanisms of FOXC2- and FOXD1-mediated regulation of the RI alpha subunit of cAMP-dependent protein kinase include release of transcriptional repression and activation by protein kinase B alpha and cAMP. J Biol Chem 2002; 277(25): 22902–22908
doi: 10.1074/jbc.M200131200 pmid: 11943768
87 Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 2013; 27(3): 234–250
doi: 10.1101/gad.211649.112 pmid: 23388824
88 Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med 2013; 19(10): 1252–1263
doi: 10.1038/nm.3361 pmid: 24100998
89 Pospisilik JA, Schramek D, Schnidar H, Cronin SJ, Nehme NT, Zhang X, Knauf C, Cani PD, Aumayr K, Todoric J, Bayer M, Haschemi A, Puviindran V, Tar K, Orthofer M, Neely GG, Dietzl G, Manoukian A, Funovics M, Prager G, Wagner O, Ferrandon D, Aberger F, Hui CC, Esterbauer H, Penninger JM. Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate. Cell 2010; 140(1): 148–160
doi: 10.1016/j.cell.2009.12.027 pmid: 20074523
90 Teperino R, Amann S, Bayer M, McGee SL, Loipetzberger A, Connor T, Jaeger C, Kammerer B, Winter L, Wiche G, Dalgaard K, Selvaraj M, Gaster M, Lee-Young RS, Febbraio MA, Knauf C, Cani PD, Aberger F, Penninger JM, Pospisilik JA, Esterbauer H. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat. Cell 2012; 151(2): 414–426
doi: 10.1016/j.cell.2012.09.021 pmid: 23063129
91 Kang S, Bajnok L, Longo KA, Petersen RK, Hansen JB, Kristiansen K, MacDougald OA. Effects of Wnt signaling on brown adipocyte differentiation and metabolism mediated by PGC-1alpha. Mol Cell Biol 2005; 25(4): 1272–1282
doi: 10.1128/MCB.25.4.1272-1282.2005 pmid: 15684380
92 Longo KA, Wright WS, Kang S, Gerin I, Chiang SH, Lucas PC, Opp MR, MacDougald OA. Wnt10b inhibits development of white and brown adipose tissues. J Biol Chem 2004; 279(34): 35503–35509
doi: 10.1074/jbc.M402937200 pmid: 15190075
93 Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem 2011; 286(15): 12983–12990
doi: 10.1074/jbc.M110.215889 pmid: 21317437
94 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(12): 6018–6027
doi: 10.1210/en.2008-0816 pmid: 18687777
95 Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, Kharitonenkov A, Flier JS, Maratos-Flier E, Spiegelman BM. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 2012; 26(3): 271–281
doi: 10.1101/gad.177857.111 pmid: 22302939
96 Chartoumpekis DV, Habeos IG, Ziros PG, Psyrogiannis AI, Kyriazopoulou VE, Papavassiliou AG. Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21. Mol Med 2011; 17(7–8): 736–740
doi: 10.2119/molmed.2011.00075 pmid: 21373720
97 Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 2008; 454(7207): 1000–1004
doi: 10.1038/nature07221 pmid: 18719589
98 Townsend KL, Suzuki R, Huang TL, Jing E, Schulz TJ, Lee K, Taniguchi CM, Espinoza DO, McDougall LE, Zhang H, He TC, Kokkotou E, Tseng YH. Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway. FASEB J 2012; 26(5): 2187–2196
doi: 10.1096/fj.11-199067 pmid: 22331196
99 Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vázquez MJ, Morgan D, Csikasz RI, Gallego R, Rodriguez-Cuenca S, Dale M, Virtue S, Villarroya F, Cannon B, Rahmouni K, López M, Vidal-Puig A. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 2012; 149(4): 871–885
doi: 10.1016/j.cell.2012.02.066 pmid: 22579288
100 Tang QQ, Otto TC, Lane MD. Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci USA 2004; 101(26): 9607–9611
doi: 10.1073/pnas.0403100101 pmid: 15210946
101 Bowers RR, Kim JW, Otto TC, Lane MD. Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: role of the BMP-4 gene. Proc Natl Acad Sci USA 2006; 103(35): 13022–13027
doi: 10.1073/pnas.0605789103 pmid: 16916928
102 Huang H, Song TJ, Li X, Hu L, He Q, Liu M, Lane MD, Tang QQ. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci USA 2009; 106(31): 12670–12675
doi: 10.1073/pnas.0906266106 pmid: 19620713
103 Huang HY, Chen SZ, Zhang WT, Wang SS, Liu Y, Li X, Sun X, Li YM, Wen B, Lei QY, Tang QQ. Induction of EMT-like response by BMP4 via up-regulation of lysyl oxidase is required for adipocyte lineage commitment. Stem Cell Res (Amst)2013; 10(3): 278–287
doi: 10.1016/j.scr.2012.12.005 pmid: 23395997
104 Qian SW, Tang Y, Li X, Liu Y, Zhang YY, Huang HY, Xue RD, Yu HY, Guo L, Gao HD, Liu Y, Sun X, Li YM, Jia WP, Tang QQ. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proc Natl Acad Sci USA 2013; 110(9): E798–E807
doi: 10.1073/pnas.1215236110 pmid: 23388637
105 Dong M, Yang X, Lim S, Cao Z, Honek J, Lu H, Zhang C, Seki T, Hosaka K, Wahlberg E, Yang J, Zhang L, L?nne T, Sun B, Li X, Liu Y, Zhang Y, Cao Y. Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis. Cell Metab 2013; 18(1): 118–129
doi: 10.1016/j.cmet.2013.06.003 pmid: 23823482
106 van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, Hansen J, J?rgensen JA, Wu J, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest 2013; 123(8): 3395–3403
doi: 10.1172/JCI68993 pmid: 23867626
107 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. J Clin Invest 2013; 123(8): 3404–3408
doi: 10.1172/JCI67803 pmid: 23867622
108 Dhaka A, Viswanath V, Patapoutian A. Trp ion channels and temperature sensation. Annu Rev Neurosci 2006; 29(1): 135–161
doi: 10.1146/annurev.neuro.29.051605.112958 pmid: 16776582
109 Nakamura K. Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol 2011; 301(5): R1207–R1228
doi: 10.1152/ajpregu.00109.2011 pmid: 21900642
110 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. Am J Clin Nutr 2009; 89(1): 45–50
doi: 10.3945/ajcn.2008.26561 pmid: 19056576
111 Ludy MJ, Moore GE, Mattes RD. The effects of capsaicin and capsiate on energy balance: critical review and meta-analyses of studies in humans. Chem Senses 2012; 37(2): 103–121
doi: 10.1093/chemse/bjr100 pmid: 22038945
112 Saito M, Yoneshiro T. Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans. Curr Opin Lipidol 2013; 24(1): 71–77
doi: 10.1097/MOL.0b013e32835a4f40 pmid: 23298960
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