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TGF-β and Metabolic Homeostasis

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TGF-β in Human Disease

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Abstract

Metabolic homeostasis is achieved via a concerted and integrative action of various organ systems. The harmonious functionality of the collaborative organs maintains tight regulation of glucose levels. This intricate balance of glucose production and utilization maintains whole body glucose homeostasis and energy balance. In disease states, such as diabetes and obesity, dysfunction in one or more organ systems disturbs the metabolic homeostasis and propagates disease pathology. Understanding the avenues that dictate metabolic homeostasis and the pathways that disrupt this harmony are thus of great medical significance. We propose that the TGF-β signaling network plays an integral role in metabolic homeostasis by virtue of its actions on several organ systems that constitute the metabolic machinery. TGF-β levels are elevated in metabolic disease, which supports the utility of therapeutics aimed at targeting the TGF-β pathway to combat these diseases. Considering the complexity of the TGF-β signaling network, a rational approach is vital to designing anti-TGF-β modalities to combat metabolic diseases.

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References

  • Alessi MC, Bastelica D, Morange P, Berthet B, Leduc I, Verdier M, Geel O, Juhan-Vague I (2000) Plasminogen activator inhibitor 1, transforming growth factor-β1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49(8):1374–1380

    PubMed  CAS  Google Scholar 

  • Andreelli F, Amouyal C, Magnan C, Mithieux G (2009) What can bariatric surgery teach us about the pathophysiology of type 2 diabetes? Diabetes Metab 35(6P2):499–507

    PubMed  CAS  Google Scholar 

  • Atit R, Sgaier SK, Mohamed OA, Taketo MM, Dufort D, Joyner AL, Niswander L, Conlon RA (2006) Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse. Dev Biol 296(1):164–176. doi:S0012-1606(06)00732-9 [pii] 10.1016/j.ydbio.2006.04.449

    PubMed  CAS  Google Scholar 

  • Attisano L, Wrana JL (2002) Signal transduction by the TGF-β superfamily. Science 296(5573):1646–1647

    PubMed  CAS  Google Scholar 

  • Bays HE, Gonzalez-Campoy JM, Bray GA, Kitabchi AE, Bergman DA, Schorr AB, Rodbard HW, Henry RR (2008) Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther 6(3):343–368. doi:10.1586/14779072.6.3.343

    PubMed  CAS  Google Scholar 

  • Bertolino P, Holmberg R, Reissmann E, Andersson O, Berggren PO, Ibanez CF (2008) Activin B receptor ALK7 is a negative regulator of pancreatic β-cell function. Proc Natl Acad Sci USA 105(20):7246–7251. doi:10.1073/pnas.0801285105

    PubMed  CAS  Google Scholar 

  • Biddinger SB, Kahn CR (2006) From mice to men: insights into the insulin resistance syndromes. Annu Rev Physiol 68(1):123–158. doi:10.1146/annurev.physiol.68.040104.124723

    PubMed  CAS  Google Scholar 

  • Bloom JD, Dutia MD, Johnson BD, Wissner A, Burns MG, Largis EE, Dolan JA, Claus TH (1992) Disodium (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3-benzodioxole-2,2-dicarboxylate  (CL 316,243). A potent β-adrenergic agonist virtually specific for β 3 receptors. A promising antidiabetic and antiobesity agent. J Med Chem 35(16):3081–3084

    PubMed  CAS  Google Scholar 

  • Borai A, Livingstone C, Kaddam I, Ferns G (2011) Selection of the appropriate method for the assessment of insulin resistance. BMC Med Res Methodol 11(1):158

    PubMed  Google Scholar 

  • Bottinger EP, Jakubczak JL, Roberts IS, Mumy M, Hemmati P, Bagnall K, Merlino G, Wakefield LM (1997) Expression of a dominant-negative mutant TGF-β type II receptor in transgenic mice reveals essential roles for TGF-β in regulation of growth and differentiation in the exocrine pancreas. EMBO J 16(10):2621–2633

    PubMed  CAS  Google Scholar 

  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84(1):277–359. doi:10.1152/physrev.00015.2003

    PubMed  CAS  Google Scholar 

  • Cannon B, Nedergaard J (2011) Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol 214(Pt 2):242–253

    PubMed  Google Scholar 

  • Chang L, Chiang SH, Saltiel AR (2004) Insulin signaling and the regulation of glucose transport. Mol Med 10(7–12):65–71. doi:10.2119/2005-00029.Saltiel

    PubMed  CAS  Google Scholar 

  • Chng Z, Vallier L, Pedersen R (2011) Activin/nodal signaling and pluripotency. Vitam Horm 85:39–58

    PubMed  CAS  Google Scholar 

  • Choy L, Derynck R (2003) Transforming growth factor-β inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J Biol Chem 278(11):9609–9619

    PubMed  CAS  Google Scholar 

  • Choy L, Skillington J, Derynck R (2000) Roles of autocrine TGF-β receptor and Smad signaling in adipocyte differentiation. J Cell Biol 149(3):667–682

    PubMed  CAS  Google Scholar 

  • Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46(11):2347–2355. doi:10.1194/jlr.M500294-JLR200

    PubMed  CAS  Google Scholar 

  • Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L, Casteilla L (1992) Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 103(Pt 4):931–942

    PubMed  CAS  Google Scholar 

  • Cusi K (2010) The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr Diab Rep 10(4):306–315. doi:10.1007/s11892-010-0122-6

    PubMed  CAS  Google Scholar 

  • Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360(15):1509–1517. doi:360/15/1509 [pii] 10.1056/NEJMoa0810780

    PubMed  CAS  Google Scholar 

  • DeFronzo RA, Tripathy D (2009) Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32(suppl 2):S157–S163. doi:10.2337/dc09-S302

    PubMed  CAS  Google Scholar 

  • Enerback S (2010) Human brown adipose tissue. Cell Metab 11(4):248–252. doi:S1550-4131(10)00078-1 [pii] 10.1016/j.cmet.2010.03.008

    PubMed  Google Scholar 

  • Fain J (2006) Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 74:443–477

    PubMed  CAS  Google Scholar 

  • Feng XH, Derynck R (2005) Specificity and versatility in tgf-β signaling through Smads. Annu Rev Cell Dev Biol 21:659–693

    PubMed  CAS  Google Scholar 

  • Frontini A, Cinti S (2010) Distribution and development of brown adipocytes in the murine and human adipose organ. Cell Metab 11(4):253–256

    PubMed  CAS  Google Scholar 

  • Gannon M (2007) BuMP-ing up insulin secretion by pancreatic β cells. Cell Metab 5(3):157–159

    PubMed  CAS  Google Scholar 

  • Gesta S, Tseng YH, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131(2):242–256

    PubMed  CAS  Google Scholar 

  • Ghorbani M, Himms-Hagen J (1997) Appearance of brown adipocytes in white adipose tissue during CL 316,243-induced reversal of obesity and diabetes in Zucker fa/fa rats. Int J Obes Relat Metab Disord 21(6):465–475

    PubMed  CAS  Google Scholar 

  • Ghorbani M, Claus TH, Himms-Hagen J (1997) Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a β3-adrenoceptor agonist. Biochem Pharmacol 54(1):121–131

    PubMed  CAS  Google Scholar 

  • Gordon KJ, Blobe GC (2008) Role of transforming growth factor-β superfamily signaling pathways in human disease. Biochim Biophys Acta 1782(4):197–228

    PubMed  CAS  Google Scholar 

  • Goulley J, Dahl U, Baeza N, Mishina Y, Edlund H (2007) BMP4-BMPR1A signaling in β cells is required for and augments glucose-stimulated insulin secretion. Cell Metab 5(3):207–219. doi:10.1016/j.cmet.2007.01.009

    PubMed  CAS  Google Scholar 

  • Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, Carter ND, Spector TD (1999) Genetic control of the circulating concentration of transforming growth factor type β1. Hum Mol Genet 8(1):93–97. doi:ddc008 [pii]

    PubMed  CAS  Google Scholar 

  • Greenberg AS, Obin MS (2006) Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 83(2):461S–465S

    PubMed  CAS  Google Scholar 

  • Greenberg AS, Obin MS (2008) Many roads lead to the lipid droplet. Cell Metab 7(6):472–473

    PubMed  CAS  Google Scholar 

  • Guo W, Wong S, Xie W, Lei T, Luo Z (2007) Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3 T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab 293(2):E576–E586. doi:10.1152/ajpendo.00523.2006

    PubMed  CAS  Google Scholar 

  • Gupta RK, Arany Z, Seale P, Mepani RJ, Ye L, Conroe HM, Roby YA, Kulaga H, Reed RR, Spiegelman BM (2010) Transcriptional control of preadipocyte determination by Zfp423. Nature 464(7288):619–623. doi:10.1038/nature08816

    PubMed  CAS  Google Scholar 

  • Gutierrez DA, Puglisi MJ, Hasty AH (2009) Impact of increased adipose tissue mass on inflammation, insulin resistance, and dyslipidemia. Curr Diab Rep 9(1):26–32

    PubMed  CAS  Google Scholar 

  • Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD, Sherwani S, Wang ZV, Landskroner-Eiger S, Dineen S, Magalang UJ, Brekken RA, Scherer PE (2009) Hypoxia-inducible factor 1{α} induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29(16):4467–4483. doi:10.1128/mcb.00192-09

    PubMed  CAS  Google Scholar 

  • Herman MA, Kahn BB (2006) Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony. J Clin Invest 116(7):1767–1775

    PubMed  CAS  Google Scholar 

  • Himms-Hagen J, Cui J, Danforth E Jr, Taatjes DJ, Lang SS, Waters BL, Claus TH (1994) Effect of CL-316,243, a thermogenic β 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 266(4 Pt 2):R1371–R1382

    PubMed  CAS  Google Scholar 

  • Ibrahim MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11(1):11–18. doi:10.1111/j.1467-789X.2009.00623.x

    PubMed  Google Scholar 

  • Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti J-F (2007) Interleukin-1B-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148(1):241–251. doi:10.1210/en.2006-0692

    PubMed  CAS  Google Scholar 

  • James D, Levine AJ, Besser D, Hemmati-Brivanlou A (2005) TGFβ/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132(6):1273–1282. doi:10.1242/dev.01706

    PubMed  CAS  Google Scholar 

  • Jimenez M, Barbatelli G, Allevi R, Cinti S, Seydoux J, Giacobino JP, Muzzin P, Preitner F (2003) β 3-adrenoceptor knockout in C57BL/6 J mice depresses the occurrence of brown adipocytes in white fat. Eur J Biochem 270(4):699–705

    PubMed  CAS  Google Scholar 

  • Jin W, Takagi T, Kanesashi SN, Kurahashi T, Nomura T, Harada J, Ishii S (2006) Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins. Dev Cell 10(4):461–471

    PubMed  CAS  Google Scholar 

  • Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH (2008) Adipocyte-derived Th2 cytokines and myeloid PPARδ regulate macrophage polarization and insulin sensitivity. Cell Metab 7(6):485–495. doi:S1550-4131(08)00112-5 [pii] 10.1016/j.cmet.2008.04.002

    PubMed  CAS  Google Scholar 

  • Karalis KP, Giannogonas P, Kodela E, Koutmani Y, Zoumakis M, Teli T (2009) Mechanisms of obesity and related pathology: linking immune responses to metabolic stress. FEBS J 276(20):5747–5754

    PubMed  CAS  Google Scholar 

  • Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M (2009) Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr 139(1):1–4. doi:jn.108.098269 [pii] 10.3945/jn.108.098269

    PubMed  CAS  Google Scholar 

  • Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, Zhang BB, Bonaldo P, Chua S, Scherer PE (2009) Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 29(6):1575–1591. doi:10.1128/mcb.01300-08

    PubMed  CAS  Google Scholar 

  • Kim SK, Hebrok M (2001) Intercellular signals regulating pancreas development and function. Genes Dev 15(2):111–127

    PubMed  CAS  Google Scholar 

  • Kim SK, MacDonald RJ (2002) Signaling and transcriptional control of pancreatic organogenesis. Curr Opin Genet Dev 12(5):540–547

    PubMed  CAS  Google Scholar 

  • Kim F, Pham M, Luttrell I, Bannerman DD, Tupper J, Thaler J, Hawn TR, Raines EW, Schwartz MW (2007a) Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res 100(11):1589–1596. doi:10.1161/circresaha.106.142851

    PubMed  CAS  Google Scholar 

  • Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, Schraw T, Durand JL, Li H, Li G, Jelicks LA, Mehler MF, Hui DY, Deshaies Y, Shulman GI, Schwartz GJ, Scherer PE (2007b) Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest 117(9):2621–2637. doi:10.1172/JCI31021

    PubMed  CAS  Google Scholar 

  • Kitisin K, Saha T, Blake T, Golestaneh N, Deng M, Kim C, Tang Y, Shetty K, Mishra B, Mishra L (2007) TGF-β signaling in development. Sci STKE 399:cm1. doi:10.1126/stke.3992007cm1

    Google Scholar 

  • Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K (2007) Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 148(2):868–877. doi:10.1210/en.2006-0687

    PubMed  CAS  Google Scholar 

  • Langin D (2009) Recruitment of brown fat and conversion of white into brown adipocytes: strategies to fight the metabolic complications of obesity? Biochim Biophys Acta 1801(3):372–376

    PubMed  Google Scholar 

  • Lee MS, Gu D, Feng L, Curriden S, Arnush M, Krahl T, Gurushanthaiah D, Wilson C, Loskutoff DL, Fox H et al (1995) Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factor-β 1. Am J Pathol 147(1):42–52

    PubMed  CAS  Google Scholar 

  • Lefterova MI, Lazar MA (2009) New developments in adipogenesis. Trends Endocrinol Metab 20(3):107–114

    PubMed  CAS  Google Scholar 

  • Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1(6):361–370

    PubMed  Google Scholar 

  • Lin HM, Lee JH, Yadav H, Kamaraju AK, Liu E, Zhigang D, Vieira A, Kim SJ, Collins H, Matschinsky F, Harlan DM, Roberts AB, Rane SG (2009) Transforming growth factor-β/Smad3 signaling regulates insulin gene transcription and pancreatic islet β-cell function. J Biol Chem 284(18):12246–12257

    PubMed  CAS  Google Scholar 

  • Loncar D (1991) Convertible adipose tissue in mice. Cell Tissue Res 266(1):149–161

    PubMed  CAS  Google Scholar 

  • Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Invest 121(6):2111–2117

    PubMed  CAS  Google Scholar 

  • Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117(1):175–184. doi:10.1172/JCI29881

    PubMed  CAS  Google Scholar 

  • Massague J, Blain SW, Lo RS (2000) TGFβ signaling in growth control, cancer, and heritable disorders. Cell 103(2):295–309

    PubMed  CAS  Google Scholar 

  • McGillicuddy FC, Harford KA, Reynolds CM, Oliver E, Claessens M, Mills KHG, Roche HM (2011) Lack of interleukin-1 receptor I (IL-1RI) protects mice from high-fat diet-induced adipose tissue inflammation coincident with improved glucose homeostasis. Diabetes 60(6):1688–1698. doi:10.2337/db10-1278

    PubMed  CAS  Google Scholar 

  • McPherron AC, Lee SJ (2002) Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest 109(5):595–601

    PubMed  CAS  Google Scholar 

  • Mishra L, Derynck R, Mishra B (2005) Transforming growth factor-β signaling in stem cells and cancer. Science 310(5745):68–71

    PubMed  CAS  Google Scholar 

  • Mullen AC, Orlando DA, Newman JJ, Loven J, Kumar RM, Bilodeau S, Reddy J, Guenther MG, DeKoter RP, Young RA (2011) Master transcription factors determine cell-type-specific responses to TGF-β signaling. Cell 147(3):565–576. doi:S0092-8674(11)01134-2 [pii] 10.1016/j.cell.2011.08.050

    PubMed  CAS  Google Scholar 

  • Nedergaard J, Cannon B (2010) The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab 11(4):268–272. doi:S1550-4131(10)00077-X [pii] 10.1016/j.cmet.2010.03.007

    PubMed  CAS  Google Scholar 

  • Nedergaard J, Bengtsson T, Cannon B (2007) Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol 293(2):E444–E452

    CAS  Google Scholar 

  • Nieto-Vazquez I, Fernandez-Veledo S, de Alvaro C, Lorenzo M (2008) Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes 57(12):3211–3221. doi:10.2337/db07-1062

    PubMed  CAS  Google Scholar 

  • Nishimura S, Manabe I, Nagasaki M, Hosoya Y, Yamashita H, Fujita H, Ohsugi M, Tobe K, Kadowaki T, Nagai R, Sugiura S (2007) Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 56(6):1517–1526. doi:10.2337/db06-1749

    PubMed  CAS  Google Scholar 

  • Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447(7148):1116–1120. doi:nature05894 [pii] 10.1038/nature05894

    PubMed  CAS  Google Scholar 

  • Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72(1):219–246. doi:10.1146/annurev-physiol-021909-135846

    PubMed  CAS  Google Scholar 

  • Park KW, Halperin DS, Tontonoz P (2008) Before they were fat: adipocyte progenitors. Cell Metab 8(6):454–457

    PubMed  CAS  Google Scholar 

  • Perfield JW, Lee Y, Shulman GI, Samuel VT, Jurczak MJ, Chang E, Xie C, Tsichlis PN, Obin MS, Greenberg AS (2010) Tumor progression locus 2 (TPL2) regulates obesity-associated inflammation and insulin resistance. Diabetes 60(4):1168–1176. doi:10.2337/db10-0715

    Google Scholar 

  • Perry JR, McCarthy MI, Hattersley AT, Zeggini E, Weedon MN, Frayling TM (2009) Interrogating type 2 diabetes genome-wide association data using a biological pathway-based approach. Diabetes 58(6):1463–1467. doi:db08-1378 [pii] 10.2337/db08-1378

    PubMed  CAS  Google Scholar 

  • Rane SG, Lee JH, Lin HM (2006) Transforming growth factor-β pathway: role in pancreas development and pancreatic disease. Cytokine Growth Factor Rev 17(1–2):107–119

    PubMed  CAS  Google Scholar 

  • Roberts AB, Wakefield LM (2003) The two faces of transforming growth factor β in carcinogenesis. Proc Natl Acad Sci USA 100(15):8621–8623. doi:10.1073/pnas.1633291100

    PubMed  CAS  Google Scholar 

  • Rosen ED, Spiegelman BM (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444(7121):847–853

    PubMed  CAS  Google Scholar 

  • Rosmond R, Chagnon M, Bouchard C, Bjorntorp P (2003) Increased abdominal obesity, insulin and glucose levels in nondiabetic subjects with a T29C polymorphism of the transforming growth factor-β1 gene. Horm Res 59(4):191–194. doi:10.1159/000069323 HRE59191 [pii]

    PubMed  CAS  Google Scholar 

  • Saberi M, Woods N-B, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, Verma IM, Olefsky JM (2009) Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab 10(5):419–429

    PubMed  CAS  Google Scholar 

  • Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, Cerletti M, McDougall LE, Giorgadze N, Tchkonia T, Schrier D, Falb D, Kirkland JL, Wagers AJ, Tseng YH (2011) Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci USA 108(1):143–148

    PubMed  CAS  Google Scholar 

  • Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454(7207):961–967

    PubMed  CAS  Google Scholar 

  • Seale P, Kajimura S, Spiegelman BM (2009) Transcriptional control of brown adipocyte development and physiological function—of mice and men. Genes Dev 23(7):788–797

    PubMed  CAS  Google Scholar 

  • Sekine N, Yamashita N, Kojima I, Miyazaki J, Ogata E (1994) Bimodal effect of transforming growth factor-β on insulin secretion in MIN6 cells. Diabetes Res Clin Pract 26(1):7–14

    PubMed  CAS  Google Scholar 

  • Senn JJ (2006) Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes. J Biol Chem 281(37):26865–26875. doi:10.1074/jbc.M513304200

    PubMed  CAS  Google Scholar 

  • Shaul ME, Bennett G, Strissel KJ, Greenberg AS, Obin MS (2010) Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet-induced obesity in mice. Diabetes 59(5):1171–1181. doi:db09-1402 [pii] 10.2337/db09-1402

    PubMed  CAS  Google Scholar 

  • Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116(11):3015–3025

    PubMed  CAS  Google Scholar 

  • Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116(7):1793–1801. doi:10.1172/JCI29069

    PubMed  CAS  Google Scholar 

  • Sjoholm A, Hellerstrom C (1991) TGF-β stimulates insulin secretion and blocks mitogenic response of pancreatic β-cells to glucose. Am J Physiol 260(5 Pt 1):C1046–C1051

    PubMed  CAS  Google Scholar 

  • Smart NG, Apelqvist AA, Gu X, Harmon EB, Topper JN, MacDonald RJ, Kim SK (2006) Conditional expression of Smad7 in pancreatic β cells disrupts TGF-β signaling and induces reversible diabetes mellitus. PLoS Biol 4(2):e39. doi:10.1371/journal.pbio.0040039

    PubMed  Google Scholar 

  • Soloveva V, Graves RA, Rasenick MM, Spiegelman BM, Ross SR (1997) Transgenic mice overexpressing the β 1-adrenergic receptor in adipose tissue are resistant to obesity. Mol Endocrinol 11(1):27–38

    PubMed  CAS  Google Scholar 

  • Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW, DeFuria J, Jick Z, Greenberg AS, Obin MS (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56(12):2910–2918. doi:10.2337/db07-0767

    PubMed  CAS  Google Scholar 

  • Strissel KJ, Defuria J, Shaul ME, Bennett G, Greenberg AS, Obin MS (2010) T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice. Obesity (Silver Spring) 18:1918–1925. doi:oby20101 [pii] 10.1038/oby.2010.1

    CAS  Google Scholar 

  • Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y, Ogawa Y (2007) Role of the toll-like receptor 4/NF-{κ}B pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27(1):84–91. doi:10.1161/01.ATV.0000251608.09329.9a

    PubMed  CAS  Google Scholar 

  • Takenaga M, Fukumoto M, Hori Y (2007) Regulated Nodal signaling promotes differentiation of the definitive endoderm and mesoderm from ES cells. J Cell Sci 120(12):2078–2090. doi:10.1242/jcs.004127

    PubMed  CAS  Google Scholar 

  • Thiebaud D, Jacot E, DeFronzo R, Maeder E, Jequier E, Felber J (1982) The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes 31:957–963

    PubMed  CAS  Google Scholar 

  • Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B (2007) Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 104(11):4401–4406

    PubMed  CAS  Google Scholar 

  • 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 (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454(7207):1000–1004

    PubMed  CAS  Google Scholar 

  • Tulachan SS, Tei E, Hembree M, Crisera C, Prasadan K, Koizumi M, Shah S, Guo P, Bottinger E, Gittes GK (2007) TGF-β isoform signaling regulates secondary transition and mesenchymal-induced endocrine development in the embryonic mouse pancreas. Dev Biol 305(2):508–521

    PubMed  CAS  Google Scholar 

  • Unger RH, Scherer PE (2010) Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab 21(6):345–352

    PubMed  CAS  Google Scholar 

  • Unger RH, Clark GO, Scherer PE, Orci L (2010) Lipid homeostasis, lipotoxicity and the metabolic syndrome. Biochim Biophys Acta 1801(3):209–214

    PubMed  CAS  Google Scholar 

  • van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360(15):1500–1508. doi:360/15/1500 [pii] 10.1056/NEJMoa0808718

    PubMed  Google Scholar 

  • Varga AC, Wrana JL (2005) The disparate role of BMP in stem cell biology. Oncogene 24(37):5713–5721

    PubMed  CAS  Google Scholar 

  • Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360(15):1518–1525. doi:360/15/1518 [pii] 10.1056/NEJMoa0808949

    PubMed  CAS  Google Scholar 

  • Watabe T, Miyazono K (2009) Roles of TGF-[β] family signaling in stem cell renewal and differentiation. Cell Res 19(1):103–115

    PubMed  CAS  Google Scholar 

  • Weigert C, Brodbeck K, Staiger H, Kausch C, Machicao F, HÃring HU, Schleicher ED (2004) Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-κB. J Biol Chem 279(23):23942–23952. doi:10.1074/jbc.M312692200

    PubMed  CAS  Google Scholar 

  • Weir GC, Bonner-Weir S (2004) Five stages of evolving β-cell dysfunction during progression to diabetes. Diabetes 53(Suppl 3):S16–S21

    PubMed  CAS  Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112(12):1796–1808. doi:10.1172/JCI19246 112/12/1796 [pii]

    PubMed  CAS  Google Scholar 

  • Willems E, Leyns L (2008) Patterning of mouse embryonic stem cell-derived pan-mesoderm by Activin A/Nodal and Bmp4 signaling requires fibroblast growth factor activity. Differentiation 76(7):745–759. doi:10.1111/j.1432-0436.2007.00257.x

    PubMed  CAS  Google Scholar 

  • Wu L, Derynck R (2009) Essential role of TGF-β signaling in glucose-induced cell hypertrophy. Dev Cell 17(1):35–48

    PubMed  CAS  Google Scholar 

  • Wu Z, Zhang W, Chen G, Cheng L, Liao J, Jia N, Gao Y, Dai H, Yuan J, Cheng L, Xiao L (2008) Combinatorial signals of activin/nodal and bone morphogenic protein regulate the early lineage segregation of human embryonic stem cells. J Biol Chem 283(36):24991–25002. doi:10.1074/jbc.M803893200

    PubMed  CAS  Google Scholar 

  • Yadav H, Rane SG (2012) TGF-β/Smad3 signaling regulates brown adipocyte induction in white adipose tissue. Front Endocrinol (Lausanne) 3:35

    CAS  Google Scholar 

  • Yadav H, Quijano C, Kamaraju Anil K, Gavrilova O, Malek R, Chen W, Zerfas P, Zhigang D, Wright Elizabeth C, Stuelten C, Sun P, Lonning S, Skarulis M, Sumner Anne E, Finkel T, Rane Sushil G (2011) Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metab 14(1):67–79. doi:10.1016/j.cmet.2011.04.013

    PubMed  CAS  Google Scholar 

  • Yamanaka Y, Friess H, Buchler M, Beger HG, Gold LI, Korc M (1993) Synthesis and expression of transforming growth factor β-1, β-2, and β-3 in the endocrine and exocrine pancreas. Diabetes 42(5):746–756

    PubMed  CAS  Google Scholar 

  • Yamaoka T, Idehara C, Yano M, Matsushita T, Yamada T, Ii S, Moritani M, Hata J, Sugino H, Noji S, Itakura M (1998) Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. J Clin Invest 102(2):294–301

    PubMed  CAS  Google Scholar 

  • Yang R, Trevillyan JM (2008) c-Jun N-terminal kinase pathways in diabetes. Int J Biochem Cell Biol 40(12):2702–2706

    PubMed  CAS  Google Scholar 

  • Zeyda M, Stulnig TM (2007) Adipose tissue macrophages. Immunol Lett 112(2):61–67

    PubMed  CAS  Google Scholar 

  • Zhang YQ, Cleary MM, Si Y, Liu G, Eto Y, Kritzik M, Dabernat S, Kayali AG, Sarvetnick N (2004) Inhibition of activin signaling induces pancreatic epithelial cell expansion and diminishes terminal differentiation of pancreatic β-cells. Diabetes 53(8):2024–2033

    PubMed  CAS  Google Scholar 

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Acknowledgment

We apologize to authors whose contributions to this field of research have not been cited or have only been indirectly cited due to space limitations. Support for this work came from funds from the NIDDK, NIH intramural program.

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Authors and Affiliations

  1. Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA

    Grace Bennett & Sushil G. Rane

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  1. Grace Bennett
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  2. Sushil G. Rane
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Correspondence to Sushil G. Rane .

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  1. , Dept Medical Biochem Microbiol, Uppsala University, Box 582, Uppsala, SE-751 23, Sweden

    Aristidis Moustakas

  2. , Interdiscip. Grad. Sch. Med. Eng., University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan

    Keiji Miyazawa

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Bennett, G., Rane, S.G. (2013). TGF-β and Metabolic Homeostasis. In: Moustakas, A., Miyazawa, K. (eds) TGF-β in Human Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54409-8_18

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