The dark side of browning

Kirstin A. Tamucci , Maria Namwanje , Lihong Fan , Li Qiang

Protein Cell ›› 2018, Vol. 9 ›› Issue (2) : 152 -163.

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Protein Cell ›› 2018, Vol. 9 ›› Issue (2) : 152 -163. DOI: 10.1007/s13238-017-0434-2
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The dark side of browning

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Abstract

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

Keywords

adipocyte / browning / beige adipocyte / thermogenesis / obesity / diabetes

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Kirstin A. Tamucci, Maria Namwanje, Lihong Fan, Li Qiang. The dark side of browning. Protein Cell, 2018, 9(2): 152-163 DOI:10.1007/s13238-017-0434-2

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References

[1]

Ab<?Pub Caret?>bas A, Blandon J, Rude J (2012) PPAR-γ agonist in treatment of diabetes: cardiovascular safety considerations. Cardiovasc Hematol Agents Med Chem 10:124–134

[2]

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

[3]

Alvarez-Dominguez JR, Bai Z, Xu D (2015) De novo reconstruction of adipose tissue transcriptomes reveals long non-coding RNA regulators of brown adipocyte development. Cell Metab 21:764–776.

[4]

Arch JRS (2002) beta(3)-Adrenoceptor agonists: potential, pitfalls and progress. Eur J Pharmacol 440:99–107

[5]

Argilés JM, Busquets S, Stemmler B, López-Soriano FJ (2014) Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 14:754–762.

[6]

Barbatelli G, Murano I, Madsen L (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298:E1244–E1253.

[7]

Barzilai N, Huffman DM, Muzumdar RH, Bartke A (2012) The critical role of metabolic pathways in aging. Diabetes 61:1315–1322.

[8]

Bauer DC, Ettinger B, Nevitt MC (2001) Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 134:561–568

[9]

Boon MR, van der Horst G, van der Pluijm G (2011) Bone morphogenetic protein 7: a broad-spectrum growth factor with multiple target therapeutic potency. Cytokine Growth Factor Rev 22:221–229.

[10]

Boon MR, van den Berg SAA, Wang Y (2013) BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. PLoS ONE 8:e74083.

[11]

Buijs JT, Henriquez NV, van Overveld PGM (2007) TGF-beta and BMP7 interactions in tumour progression and bone metastasis. Clin Exp Metastasis 24:609–617.

[12]

Bundgaard H, Axelsson A, Hartvig Thomsen J (2016) The-firstin-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial. Eur J Heart Fail.

[13]

Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359

[14]

Carreira AC, Lojudice FH, Halcsik E (2014) Bone morphogenetic proteins: facts, challenges, and future perspectives. J Dent Res 93:335–345.

[15]

Cederberg A, Gronning LM, Ahren B (2001) FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 106:563–573

[16]

Chau MDL, Gao J, Yang Q (2010) Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci USA 107:12553–12558.

[17]

Chondronikola M, Volpi E, Børsheim E (2014) Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes 63:4089–4099.

[18]

Chondronikola M, Volpi E, Børsheim E (2016) Brown adipose tissue activation is linked to distinct systemic effects on lipid metabolism in humans. Cell Metab 23:1200–1206.

[19]

Cohen P, Levy JD, Zhang Y (2014) Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156:304–316.

[20]

Coskun T, Bina HA, Schneider MA (2008) Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149:6018–6027.

[21]

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

[22]

Cypess AM, Weiner LS, Roberts-Toler C (2015) Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab 21:33–38.

[23]

Das SK, Eder S, Schauer S (2011) Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333:233–238.

[24]

Dodd GT, Decherf S, Loh K (2015) Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell 160:88–104.

[25]

Dutchak PA, Katafuchi T, Bookout AL (2012) Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones. Cell 148:556–567.

[26]

Elias I, Franckhauser S, Ferré T (2012) Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance. Diabetes 61:1801–1813.

[27]

Farmer SR (2006) Transcriptional control of adipocyte formation. Cell Metab 4:263–273.

[28]

Fearon KCH, Glass DJ, Guttridge DC (2012) Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab 16:153–166.

[29]

Fearon K, Arends J, Baracos V (2013) Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 10:90–99.

[30]

Ferrannini G, Namwanje M, Fang B (2016) Genetic backgrounds determine brown remodeling of white fat in rodents. Mol Metab 5:948–958.

[31]

Ferrara N, Adamis AP (2016) Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov 15:385–403.

[32]

Fischer K, Ruiz HH, Jhun K (2017) Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat Med 23:623–630.

[33]

Fisher FM, Kleiner S, Douris N (2012) FGF21 regulates PGC-1 {alpha} and browning of white adipose tissues in adaptive thermogenesis. Genes & Development 26:271–281.

[34]

Frontini A, Vitali A, Perugini J (2013) White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta 1831:950–959.

[35]

Gaich G, Chien JY, Fu H (2013) The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18:333–340.

[36]

Gerhart-Hines Z, Feng D, Emmett MJ (2013) The nuclear receptor Rev-erbα controls circadian thermogenic plasticity. Nature 503:410–413.

[37]

Gesta S, Tseng YH, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131:242–256.

[38]

Grefhorst A, van den Beukel JC, van Houten ELA (2015) Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice. Biol Sex Differ 6:7.

[39]

Guerra C, Koza RA, Yamashita H (1998) Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 102:412–420

[40]

Guilherme A, Virbasius JV, Puri V, Czech MP (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 9:367–377.

[41]

Guntur AR, Doucette CR, Rosen CJ (2015) PTHrp comes full circle in cancer biology. Bonekey Rep 4:621.

[42]

Gupta RK, Arany Z, Seale P (2010) Transcriptional control of preadipocyte determination by Zfp423. Nature 464:619–623.

[43]

Hankir MK, Cowley MA, Fenske WK (2016) A BAT-centric approach to the treatment of diabetes: turn on the brain. Cell Metab 24:31–40.

[44]

Himms-Hagen J, Cui J, Danforth EJ (1994) Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 266: R1371–R1382

[45]

Himms-Hagen J, Melnyk A, Zingaretti MC (2000) Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Physiol Cell Physiol 279:C670–C681

[46]

Inagaki T, Dutchak P, Zhao G (2007) Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab 5:415–425.

[47]

Inagaki T, Lin VY, Goetz R (2008) Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab 8:77–83.

[48]

Jeschke MG (2009) The hepatic response to thermal injury: is the liver important for postburn outcomes? Mol Med 15:337–351.

[49]

Jeschke MG, Gauglitz GG, Finnerty CC (2014) Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories. Ann Surg 259:814–823.

[50]

Kernan WN, Viscoli CM, Furie KL (2016) Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 374:1321–1331.

[51]

Kharitonenkov A, Shiyanova TL, Koester A (2005) FGF-21 as a novel metabolic regulator. J Clin Invest 115:1627–1635.

[52]

Kharitonenkov A, Wroblewski VJ, Koester A (2007) The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148:774–781.

[53]

Kim JK, Kim H-J, Park S-Y (2005) Adipocyte-specific overexpression of FOXC2 prevents diet-induced increases in intramuscular fatty acyl CoA and insulin resistance. Diabetes 54:1657–1663

[54]

Kim J-Y, van de Wall E, Laplante M (2007) Obesityassociated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest 117:2621–2637.

[55]

Kim H-J, Cho H, Alexander R (2014) MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes. Diabetes 63:4045–4056.

[56]

Kir S, White JP, Kleiner S (2014) Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 513:100–104.

[57]

Kir S, Komaba H, Garcia AP (2016) PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab 23:315–323.

[58]

Knowler WC, Hamman RF, Edelstein SL (2005) Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. Diabetes 54:1150–1156

[59]

Kong X, Banks A, Liu T (2014) IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 158:69–83.

[60]

Kopecky J, Clarke G, Enerback S (1995) Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest 96:2914–2923.

[61]

Kulp GA, Herndon DN, Lee JO (2010) Extent and magnitude of catecholamine surge in pediatric burned patients. Shock 33:369–374.

[62]

Lee Y-H, Petkova AP, Mottillo EP, Granneman JG (2012) In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding. Cell Metab 15:480–491.

[63]

Li D, Zhang F, Zhang X (2016) Distinct functions of PPARγ isoforms in regulating adipocyte plasticity. Biochem Biophys Res Commun 481:132–138.

[64]

Lim YC, Chia SY, Jin S (2016) Dynamic DNA methylation landscape defines brown and white cell specificity during adipogenesis. Mol Metab 5:1033–1041.

[65]

Lin JZ, Martagón AJ, Cimini SL (2015) Pharmacological activation of thyroid hormone receptors elicits a functional conversion of white to brown fat. Cell Rep 13:1528–1537.

[66]

Liu T, Kong D, Shah BP (2012) Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 73:511–522.

[67]

Long JZ, Svensson KJ, Tsai L (2014) A smooth muscle-like origin for beige adipocytes. Cell Metab 19:810–820.

[68]

Lu X, Ji Y, Zhang L (2012) Resistance to obesity by repression of VEGF gene expression through induction of brown-like adipocyte differentiation. Endocrinology 153:3123–3132.

[69]

Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184.

[70]

Ma X, Xu L, Gavrilova O, Mueller E (2014) Role of forkhead box protein A3 in age-associated metabolic decline. Proc Natl Acad Sci USA 111:14289–14294.

[71]

Ma X, Xu L, Mueller E (2015) Calorie hoarding and thrifting: Foxa3 finds a way. Adipocyte 4:325–328.

[72]

Maioli E, Fortino V, Torricelli C (2002) Effect of parathyroid hormone-related protein on fibroblast proliferation and collagen metabolism in human skin. Exp Dermatol 11:302–310

[73]

McDonald ME, Li C, Bian H (2015) Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes. Cell 160:105–118.

[74]

Medina-Gomez G, Calvo RM, Obregon MJ (2008) Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis. Am J Physiol Endocrinol Metab 294:E688–E697.

[75]

Moghri J, Akbari Sari A, Yousefi M (2013) Is scores derived from the most internationally applied patient safety culture assessment tool correct? Iran J Public Health 42:1058–1066

[76]

Moolman JA (2002) Thyroid hormone and the heart. Cardiovasc J S Afr 13:159–163

[77]

Mullur R, Liu Y-Y, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94:355–382.

[78]

Murphy E, Williams GR (2004) The thyroid and the skeleton. Clin Endocrinol (Oxf) 61:285–298.

[79]

Nedergaard J, Cannon B (2010) The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab 11:268–272.

[80]

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

[81]

Ng Y, Tan S-X, Chia SY (2017) HOXC10 suppresses browning of white adipose tissues. Exp Mol Med 49:e292.

[82]

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

[83]

Ohno H, Shinoda K, Spiegelman BM, Kajimura S (2012) PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab 15:395–404.

[84]

Ortega-Molina A, Efeyan A, Lopez-Guadamillas E (2012) Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab 15:382–394.

[85]

Patsouris D, Qi P, Abdullahi A (2015) Burn induces browning of the subcutaneous white adipose tissue in mice and humans. Cell Rep 13:1538–1544.

[86]

Pedroso FE, Spalding PB, Cheung MC (2012) Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia. J Cachexia Sarcopenia Muscle 3 (3):199–211

[87]

Petrovic N, Walden TB, Shabalina IG (2010) Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285:7153–7164.

[88]

Petruzzelli M, Schweiger M, Schreiber R (2014) A switch from white to brown fat increases energy expenditure in cancerassociated cachexia. Cell Metab 20:433–447.

[89]

Qiang L, Wang L, Kon N (2012) Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell 150:620–632.

[90]

Qiao L, Yoo HS, Bosco C (2014) Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice. Diabetologia 57:1027–1036.

[91]

Rajakumari S, Wu J, Ishibashi J (2013) EBF2 determines and maintains brown adipocyte identity. Cell Metab 17:562–574.

[92]

Randall SM, Fear MW, Wood FM (2015) Long-term musculoskeletal morbidity after adult burn injury: a population-based cohort study. BMJ Open 5:e009395.

[93]

Rogers NH, Landa A, Park S, Smith RG (2012) Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue. Aging Cell 11:1074–1083.

[94]

Rong JX, Qiu Y, Hansen MK (2007) Adipose mitochondrial biogenesis is suppressed in db/db and high-fat diet-fed mice and improved by rosiglitazone. Diabetes 56:1751–1760.

[95]

Rosenwald M, Perdikari A, Rülicke T, Wolfrum C (2013) Bidirectional interconversion of brite and white adipocytes. Nat Cell Biol 15:659–667.

[96]

Rothwell NJ, Stock MJ (1979) A role for brown adipose tissue in dietinduced thermogenesis. Nature 281:31–35

[97]

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.

[98]

Sanchez-Gurmaches J, Hung C-M, Sparks CA (2012) PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab 16:348–362.

[99]

Seale P, Kajimura S, Yang W (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6:38–54

[100]

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

[101]

Seale P, Conroe HM, Estall J (2011) Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121:96–105.

[102]

Sell H, Berger JP, Samson P (2004) Peroxisome proliferator-activated receptor gamma agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice. Endocrinology 145:3925–3934.

[103]

Shah P, Mudaliar S (2010) Pioglitazone: side effect and safety profile. Expert Opin Drug Saf 9:347–354.

[104]

Shao M, Ishibashi J, Kusminski CM (2016) Zfp423 maintains white adipocyte identity through suppression of the beige cell thermogenic gene program. Cell Metab 23:1167–1184.

[105]

Sidossis LS, Porter C, Saraf MK (2015) Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metab 22:219–227.

[106]

Smith RE, Hock RJ (1963) Brown fat: thermogenic effector of arousal in hibernators. Science 140:199–200

[107]

Soccio RE, Chen ER, Lazar MA (2014) Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab 20:573–591.

[108]

Stefl B, Janovská A, Hodný Z (1998) Brown fat is essential for cold-induced thermogenesis but not for obesity resistance in aP2-Ucp mice. Am J Physiol 274:E527–E533

[109]

Sun K, Wernstedt Asterholm I, Kusminski CM (2012) Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc Natl Acad Sci USA 109:5874–5879.

[110]

Sung H-K, Doh K-O, Son JE (2013) Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab 17:61–72.

[111]

Tchkonia T, Morbeck DE, Von Zglinicki T (2010) Fat tissue, aging, and cellular senescence. Aging Cell 9:667–684.

[112]

Tseng YH, Kokkotou E, Schulz TJ (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000–1004

[113]

Van Gaal LF, Mertens IL, De Block CE (2006) Mechanisms linking obesity with cardiovascular disease. Nature 444:875–880.

[114]

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

[115]

Vegiopoulos A, Müller-Decker K, Strzoda D (2010) Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328:1158–1161.

[116]

Vernochet C, Peres SB, Davis KE (2009) C/EBPalpha and the corepressors CtBP1 and CtBP2 regulate repression of select visceral white adipose genes during induction of the brown phenotype in white adipocytes by peroxisome proliferator-activated receptor gamma agonists. Mol Cell Biol 29:4714–4728.

[117]

Villanueva CJ, Waki H, Godio C (2011) TLE3 is a dual-function transcriptional coregulator of adipogenesis. Cell Metab 13:413–427.

[118]

Villanueva CJ, Vergnes L, Wang J (2013) Adipose subtypeselective recruitment of TLE3 or Prdm16 by PPARγ specifies lipid storage versus thermogenic gene programs. Cell Metab 17:423–435.

[119]

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

[120]

Wada S, Neinast M, Jang C (2016) The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue. Genes Dev 30:2551–2564.

[121]

Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19:1338–1344.

[122]

Wei W, Dutchak PA, Wang X (2012) Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ. Proc Natl Acad Sci USA 109:3143–3148.

[123]

Wente W, Efanov AM, Brenner M (2006) Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes 55:2470–2478.

[124]

Weyer C, Tataranni PA, Snitker S (1998) Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans. Diabetes 47:1555–1561

[125]

Wilson-Fritch L, Nicoloro S, Chouinard M (2004) Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114:1281–1289.

[126]

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

[127]

Xiu F, Catapano M, Diao L (2015) Prolonged endoplasmic reticulum-stressed hepatocytes drive an alternative macrophage polarization. Shock 44:44–51.

[128]

Xiu F, Diao L, Qi P (2016) Palmitate differentially regulates the polarization of differentiating and differentiated macrophages. Immunology 147:82–96.

[129]

Yan M, Audet-Walsh É, Manteghi S (2016) Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα. Genes Dev 30:1034–1046.

[130]

Yoneshiro T, Aita S, Matsushita M (2011) Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 19:1755–1760.

[131]

Zechner R, Zimmermann R, Eichmann TO (2012) FAT SIGNALS—lipases and lipolysis in lipid metabolism and signaling. Cell Metab 15:279–291.

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