Cytokines and inflammation in adipogenesis: an updated review

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNFα and IL-1β) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

This is a preview of subscription content, access via your institution.

References

  1. 1.

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

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014; 156(1–2): 20–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol 2012; 13(8): 707–712

    Article  CAS  Google Scholar 

  4. 4.

    Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112(12): 1796–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 2011; 12(11): 722–734

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Cawthorn WP, Heyd F, Hegyi K, Sethi JK. Tumour necrosis factor-α inhibits adipogenesis via a β-catenin/TCF4(TCF7L2)-dependent pathway. Cell Death Differ 2007; 14(7): 1361–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Isakson P, Hammarstedt A, Gustafson B, Smith U. Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-α, and inflammation. Diabetes 2009; 58(7): 1550–1557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Xu H, Sethi JK, Hotamisligil GS. Transmembrane tumor necrosis factor (TNF)-α inhibits adipocyte differentiation by selectively activating TNF receptor 1. J Biol Chem 1999; 274(37): 26287–26295

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Chae GN, Kwak SJ. NF-κB is involved in the TNF-α induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARgamma expression. Exp Mol Med 2003; 35(5): 431–437

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Gagnon A, Foster C, Landry A, Sorisky A. The role of interleukin 1β in the anti-adipogenic action of macrophages on human preadipocytes. J Endocrinol 2013; 217(2): 197–206

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Martinez-Martinez E, Cachofeiro V, Rousseau E, Alvarez V, Calvier L, Fernandez-Celis A, Leroy C, Miana M, Jurado-Lopez R, Briones AM, Jaisser F, Zannad F, Rossignol P, Lopez-Andres N. Interleukin-33/ST2 system attenuates aldosterone-induced adipogenesis and inflammation. Mol Cell Endocrinol 2015; 411:20–27

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, Xu D, Sattar N, McInnes IB, Liew FY. Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res 2010; 107(5): 650–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    van Asseldonk EJ, Stienstra R, Koenen TB, van Tits LJ, Joosten LA, Tack CJ, Netea MG. The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation. Obesity (Silver Spring) 2010; 18(11): 2234–2236

    Article  CAS  Google Scholar 

  14. 14.

    Somm E, Henrichot E, Pernin A, Juge-Aubry CE, Muzzin P, Dayer JM, Nicklin MJH, Meier CA. Decreased fat mass in interleukin-1 receptor antagonist-deficient mice—impact on adipogenesis, food intake, and energy expenditure. Diabetes 2005; 54(12): 3503–3509

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Ballak DB, van Diepen JA, Moschen AR, Jansen HJ, Hijmans A, Groenhof GJ, Leenders F, Bufler P, Boekschoten MV, Muller M, Kersten S, Li S, Kim S, Eini H, Lewis EC, Joosten LA, Tilg H, Netea MG, Tack CJ, Dinarello CA, Stienstra R. IL-37 protects against obesity-induced inflammation and insulin resistance. Nat Commun 2014; 5:4711 PMID: 25182023

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Almuraikhy S, Kafienah W, Bashah M, Diboun I, Jaganjac M, Al-Khelaifi F, Abdesselem H, Mazloum NA, Alsayrafi M, Mohamed-Ali V, Elrayess MA. Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance. Diabetologia 2016; 59(11): 2406–2416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Lagathu C, Bastard JP, Auclair M, Maachi M, Capeau J, Caron M. Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem Biophys Res Commun 2003; 311(2): 372–379

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Bahar B, O’Doherty JV, Sweeney T. A potential role of IL-6 in the chito-oligosaccharide-mediated inhibition of adipogenesis. Br J Nutr 2011; 106(8): 1142–1153

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Keller DC, Du XX, Srour EF, Hoffman R, Williams DA. Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human long-term marrow cultures. Blood 1993; 82(5): 1428–1435

    CAS  PubMed  Google Scholar 

  20. 20.

    Kawashima I, Ohsumi J, Mita-Honjo K, Shimoda-Takano K, Ishikawa H, Sakakibara S, Miyadai K, Takiguchi Y. Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11. FEBS Lett 1991; 283(2): 199–202

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Miyaoka Y, Tanaka M, Naiki T, Miyajima A. Oncostatin M inhibits adipogenesis through the RAS/ERK and STAT5 signaling pathways. J Biol Chem 2006; 281(49): 37913–37920

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    White UA, Stewart WC, Mynatt RL, Stephens JM. Neuropoietin attenuates adipogenesis and induces insulin resistance in adipocytes. J Biol Chem 2008; 283(33): 22505–22512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Tsao CH, Shiau MY, Chuang PH, Chang YH, Hwang J. Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis. J Lipid Res 2014; 55(3): 385–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    López S. Interleukin-15 increases calcineurin expression in 3T3- L1 cells: possible involvement on in vivo adipocyte differentiation. Int J Mol Med 2009; 24(04): 453–458

    Google Scholar 

  25. 25.

    Lee M, Song SJ, Choi MS, Yu RN, Park T. IL-7 receptor deletion ameliorates diet-induced obesity and insulin resistance in mice. Diabetologia 2015; 58(10): 2361–2370

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Ahmed M, Gaffen SL. IL-17 in obesity and adipogenesis. Cytokine Growth Factor Rev 2010; 21(6): 449–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Ahmed M, Gaffen SL. IL-17 inhibits adipogenesis in part via C/ EBPα, PPARγ and Kruppel-like factors. Cytokine 2013; 61(3): 898–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Zuniga LA, Shen WJ, Joyce-Shaikh B, Pyatnova EA, Richards AG, Thom C, Andrade SM, Cua DJ, Kraemer FB, Butcher EC. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol 2010; 185(11): 6947–6959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Chang EJ, Lee SK, Song YS, Jang YJ, Park HS, Hong JP, Ko AR, Kim DY, Kim JH, Lee YJ, Heo YS. IL-34 is associated with obesity, chronic inflammation, and insulin resistance. J Clin Endocrinol Metab 2014; 99(7): E1263–E1271

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Lee K, Um SH, Rhee DK, Pyo S. Interferon-α inhibits adipogenesis via regulation of JAK/STAT1 signaling. Biochim Biophys Acta 2016; 1860(11 11 Pt A): 2416–2427

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Vidal C, Bermeo S, Li W, Huang D, Kremer R, Duque G. Interferon γ inhibits adipogenesis in vitro and prevents marrow fat infiltration in oophorectomized mice. Stem Cells 2012; 30(5): 1042–1048

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Todoric J, Strobl B, Jais A, Boucheron N, Bayer M, Amann S, Lindroos J, Teperino R, Prager G, Bilban M, Ellmeier W, Krempler F, Muller M, Wagner O, Patsch W, Pospisilik JA, Esterbauer H. Cross-talk between interferon-γ and hedgehog signaling regulates adipogenesis. Diabetes 2011; 60(6): 1668–1676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Younce CW, Azfer A, Kolattukudy PE. MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-adipocytes without peroxisome proliferator-activated receptor γ. J Biol Chem 2009; 284(40): 27620–27628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Hemmrich K, Thomas GP, Abberton KM, Thompson EW, Rophael JA, Penington AJ, Morrison WA. Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity. Obesity (Silver Spring) 2007; 15(12): 2951–2957

    Article  CAS  Google Scholar 

  35. 35.

    Meerson A, Traurig M, Ossowski V, Fleming JM, Mullins M, Baier LJ. Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-α. Diabetologia 2013; 56(9): 1971–1979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Liu S, Yang Y, Wu J. TNFα-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors. Biochem Biophys Res Commun 2011; 414(3): 618–624

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Xie H, Lim B, Lodish HF. MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes 2009; 58(5): 1050–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Gaur U, Aggarwal BB. Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol 2003; 66(8): 1403–1408

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Aggarwal BB. Tumour necrosis factors receptor associated signalling molecules and their role in activation of apoptosis, JNK and NF-κB. Ann Rheum Dis 2000; 59 (Suppl 1): i6–i16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Kaufman DR, Choi Y. Signaling by tumor necrosis factor receptors: pathways, paradigms and targets for therapeutic modulation. Int Rev Immunol 1999; 18(4): 405–427

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001; 11(9): 372–377

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Fain JN, Bahouth SW, Madan AK. TNFα release by the nonfat cells of human adipose tissue. Int J Obes Relat Metab Disord 2004; 28(4): 616–622

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 1993; 259(5091): 87–91

    Article  CAS  Google Scholar 

  44. 44.

    Borst SE. The role of TNF-α in insulin resistance. Endocrine 2004; 23(2–3): 177–182

    Article  CAS  PubMed  Google Scholar 

  45. 45.

    Moller DE. Potential role of TNF-α in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 2000; 11(6): 212–217

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Stephens JM, Lee J, Pilch PF. Tumor necrosis factor-α-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem 1997; 272(2): 971–976

    Article  CAS  PubMed  Google Scholar 

  47. 47.

    Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest 1995; 95(5): 2409–2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM. TNF-α is a predictor of insulin resistance in human pregnancy. Diabetes 2002; 51(7): 2207–2213

    Article  CAS  PubMed  Google Scholar 

  49. 49.

    Lang CH, Dobrescu C, Bagby GJ. Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology 1992; 130(1): 43–52

    Article  CAS  PubMed  Google Scholar 

  50. 50.

    Palacios-Ortega S, Varela-Guruceaga M, Algarabel M, Ignacio Milagro F, Alfredo Martinez J, de Miguel C. Effect of TNF-α on caveolin-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes. Cell Physiol Biochem 2015; 36(4): 1499–1516

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 1997; 389(6651): 610–614

    Article  CAS  Google Scholar 

  52. 52.

    Hu E, Kim JB, Sarraf P, Spiegelman BM. Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARγ. Science 1996; 274(5295): 2100–2103

    Article  CAS  PubMed  Google Scholar 

  53. 53.

    Ohsumi J, Sakakibara S, Yamaguchi J, Miyadai K, Yoshioka S, Fujiwara T, Horikoshi H, Serizawa N. Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells. Endocrinology 1994; 135(5): 2279–2282

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Bogacka I, Xie H, Bray GA, Smith SR. The effect of pioglitazone on peroxisome proliferator-activated receptor-γ target genes related to lipid storage in vivo. Diabetes Care 2004; 27(7): 1660–1667

    Article  CAS  PubMed  Google Scholar 

  55. 55.

    Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A. Adipogenesis and WNT signalling. Trends Endocrinol Metab 2009; 20(1): 16–24

    Article  CAS  PubMed  Google Scholar 

  56. 56.

    Zhang B, Berger J, Hu E, Szalkowski D, White-Carrington S, Spiegelman BM, Moller DE. Negative regulation of peroxisome proliferator-activated receptor-γ gene expression contributes to the antiadipogenic effects of tumor necrosis factor-α. Mol Endocrinol 1996; 10(11): 1457–1466

    CAS  PubMed  Google Scholar 

  57. 57.

    Ruan H, Hacohen N, Golub TR, Van Parijs L, Lodish HF. Tumor necrosis factor-α suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-κB activation by TNF-α is obligatory. Diabetes 2002; 51(5): 1319–1336

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Tang X, Guilherme A, Chakladar A, Powelka AM, Konda S, Virbasius JV, Nicoloro SM, Straubhaar J, Czech MP. An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARγ, adipogenesis, and insulin-responsive hexose transport. Proc Natl Acad Sci USA 2006; 103(7): 2087–2092

    Article  CAS  PubMed  Google Scholar 

  59. 59.

    Guilherme A, Tesz GJ, Guntur KVP, Czech MP. Tumor necrosis factor-α induces caspase-mediated cleavage of peroxisome proliferator- activated receptor in adipocytes. J Biol Chem 2009; 284(25): 17082–17091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Gong ML, Liu CG, Zhang L, Zhang HB, Pan J. Loss of the TNFα function inhibits Wnt/β-catenin signaling, exacerbates obesity development in adolescent spontaneous obese mice. Mol Cell Biochem 2014; 391(1–2): 59–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Arner P, Kulyte A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat Rev Endocrinol 2015; 11(5): 276–288

    Article  CAS  PubMed  Google Scholar 

  62. 62.

    Price NL, Fernandez-Hernando C. miRNA regulation of white and brown adipose tissue differentiation and function. Biochim Biophys Acta 2016; 1861(12): 2104–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Zhu L, Chen L, Shi CM, Xu GF, Xu LL, Zhu LL, Guo XR, Ni YH, Cui Y, Ji CB. miR-335, an adipogenesis-related microRNA, is involved in adipose tissue inflammation. Cell Biochem Biophys 2014; 68(2): 283–290

    Article  CAS  PubMed  Google Scholar 

  64. 64.

    Zhu Y, Zhang X, Ding X, Wang H, Chen X, Zhao H, Jia Y, Liu S, Liu Y. miR-27 inhibits adipocyte differentiation via suppressing CREB expression. Acta Biochim Biophys Sin (Shanghai) 2014; 46(7): 590–596

    Article  CAS  PubMed  Google Scholar 

  65. 65.

    Xu G, Ji C, Shi C, Fu H, Zhu L, Zhu L, Xu L, Chen L, Feng Y, Zhao Y, Guo X. Modulation of hsa-miR-26b levels following adipokine stimulation. Mol Biol Rep 2013; 40(5): 3577–3582

    Article  CAS  PubMed  Google Scholar 

  66. 66.

    Song G, Xu G, Ji C, Shi C, Shen Y, Chen L, Zhu L, Yang L, Zhao Y, Guo X. The role of microRNA-26b in human adipocyte differentiation and proliferation. Gene 2014; 533(2): 481–487

    Article  CAS  PubMed  Google Scholar 

  67. 67.

    Xu LL, Shi CM, Xu GF, Chen L, Zhu LL, Zhu L, Guo XR, Xu MY, Ji CB. TNF-α, IL-6, and leptin increase the expression of miR-378, an adipogenesis-related microRNA in human adipocytes. Cell Biochem Biophys 2014; 70(2): 771–776

    Article  CAS  PubMed  Google Scholar 

  68. 68.

    Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity 2013; 39(6): 1003–1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Simons PJ, van den Pangaart PS, van Roomen CP, Aerts JM, Boon L. Cytokine-mediated modulation of leptin and adiponectin secretion during in vitro adipogenesis: evidence that tumor necrosis factor-α- and interleukin-1β-treated human preadipocytes are potent leptin producers. Cytokine 2005; 32(2): 94–103

    Article  CAS  PubMed  Google Scholar 

  70. 70.

    Tack CJ, Stienstra R, Joosten LAB, Netea MG. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family. Immunol Rev 2012; 249(1): 239–252

    Article  CAS  PubMed  Google Scholar 

  71. 71.

    Solt LA, Madge LA, Orange JS, May MJ. Interleukin-1-induced NF-κB activation is NEMO-dependent but does not require IKKβ. J Biol Chem 2007; 282(12): 8724–8733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Tanti JF, Jager J. Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr Opin Pharmacol 2009; 9(6): 753–762

    Article  CAS  PubMed  Google Scholar 

  73. 73.

    Wood IS, Wang B, Jenkins JR, Trayhurn P. The pro-inflammatory cytokine IL-18 is expressed in human adipose tissue and strongly upregulated by TNFα in human adipocytes. Biochem Biophys Res Commun 2005; 337(2): 422–429

    Article  CAS  PubMed  Google Scholar 

  74. 74.

    Schernthaner GH, Kopp HP, Kriwanek S, Krzyzanowska K, Satler M, Koppensteiner R, Schernthaner G. Effect of massive weight loss induced by bariatric surgery on serum levels of interleukin-18 and monocyte-chemoattractant-protein-1 in morbid obesity. Obes Surg 2006; 16(6): 709–715

    Article  PubMed  Google Scholar 

  75. 75.

    Moschen AR, Molnar C, Enrich B, Geiger S, Ebenbichler CF, Tilg H. Adipose and liver expression of interleukin (IL)-1 family members in morbid obesity and effects of weight loss. Mol Med 2011; 17(7–8): 840–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Netea MG, Joosten LA, Lewis E, Jensen DR, Voshol PJ, Kullberg BJ, Tack CJ,van Krieken H, Kim SH, Stalenhoef AF, van de Loo FA, Verschueren I, Pulawa L, Akira S, Eckel RH, Dinarello CA, van den Berg W, van der Meer JW. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat Med 2006; 12(6): 650–656

    Article  CAS  PubMed  Google Scholar 

  77. 77.

    Zorrilla EP, Sanchez-Alavez M, Sugama S, Brennan M, Fernandez R, Bartfai T, Conti B. Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc Natl Acad Sci USA 2007; 104(26): 11097–11102

    Article  CAS  Google Scholar 

  78. 78.

    Yang YS, Li XY, Hong J, Gu WQ, Zhang YF, Yang J, Song HD, Chen JL, Ning G. Interleukin-18 enhances glucose uptake in 3T3-L1 adipocytes. Endocrine 2007; 32(3): 297–302

    Article  CAS  PubMed  Google Scholar 

  79. 79.

    Ballak DB, Stienstra R, Tack CJ, Dinarello CA, van Diepen JA. IL-1 family members in the pathogenesis and treatment of metabolic disease: focus on adipose tissue inflammation and insulin resistance. Cytokine 2015; 75(2): 280–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Murphy AJ, Kraakman MJ, Kammoun HL, Dragoljevic D, Lee MK, Lawlor KE, Wentworth JM, Vasanthakumar A, Gerlic M, Whitehead LW, DiRago L, Cengia L, Lane RM, Metcalf D, Vince JE, Harrison LC, Kallies A, Kile BT, Croker BA, Febbraio MA, Masters SL. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome. Cell Metab 2016; 23(1): 155–164

    Article  CAS  Google Scholar 

  81. 81.

    Lindegaard B, Matthews VB, Brandt C, Hojman P, Allen TL, Estevez E, Watt MJ, Bruce CR, Mortensen OH, Syberg S, Rudnicka C, Abildgaard J, Pilegaard H, Hidalgo J, Ditlevsen S, Alsted TJ, Madsen AN, Pedersen BK, Febbraio MA. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice. Diabetes 2013; 62(9): 3064–3074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Han JM, Wu D, Denroche HC, Yao Y, Verchere CB, Levings MK. IL-33 reverses an obesity-induced deficit in visceral adipose tissue ST2+ T regulatory cells and ameliorates adipose tissue inflammation and insulin resistance. J Immunol 2015; 194(10): 4777–4783

    Article  CAS  PubMed  Google Scholar 

  83. 83.

    Wood IS, Wang B, Trayhurn P. IL-33, a recently identified interleukin-1 gene family member, is expressed in human adipocytes. Biochem Biophys Res Commun 2009; 384(1): 105–109

    Article  CAS  PubMed  Google Scholar 

  84. 84.

    Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 2013; 210(3): 535–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Zeyda M, Wernly B, Demyanets S, Kaun C, Hammerle M, Hantusch B, Schranz M, Neuhofer A, Itariu BK, Keck M, Prager G, Wojta J, Stulnig TM. Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue. Int J Obes 2013; 37(5): 658–665

    Article  CAS  Google Scholar 

  86. 86.

    Molofsky AB, Savage AK, Locksley RM. Interleukin-33 in tissue homeostasis, injury, and inflammation. Immunity 2015; 42(6): 1005–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, Thome JJ, Farber DL, Lutfy K, Seale P, Artis D. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 2015; 519(7542): 242–246

    Article  CAS  Google Scholar 

  88. 88.

    White UA, Stephens JM. The gp130 receptor cytokine family: regulators of adipocyte development and function. Curr Pharm Des 2011; 17(4): 340–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Pal M, Febbraio MA, Whitham M. From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation. Immunol Cell Biol 2014; 92(4): 331–339

    Article  CAS  Google Scholar 

  90. 90.

    Kraakman MJ, Allen TL, Whitham M, Iliades P, Kammoun HL, Estevez E, Lancaster GI, Febbraio MA. Targeting gp130 to prevent inflammation and promote insulin action. Diabetes Obes Metab 2013; 15(Suppl 3): 170–175

    Article  CAS  PubMed  Google Scholar 

  91. 91.

    Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulinresistant subjects. J Biol Chem 2003; 278(46): 45777–45784

    Article  CAS  PubMed  Google Scholar 

  92. 92.

    Ishimoto K, Iwata T, Taniguchi H, Mizusawa N, Tanaka E, Yoshimoto K. D-dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in preadipocytes. Cytokine 2012; 60(3): 772–777

    Article  CAS  PubMed  Google Scholar 

  93. 93.

    Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MA. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 2006; 55(10): 2688–2697

    Article  CAS  PubMed  Google Scholar 

  94. 94.

    Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 2002; 8(1): 75–79

    Article  CAS  PubMed  Google Scholar 

  95. 95.

    Fritsche L, Hoene M, Lehmann R, Ellingsgaard H, Hennige AM, Pohl AK, Haring HU, Schleicher ED, Weigert C. IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise. Diabetologia 2010; 53(8): 1732–1742

    Article  CAS  PubMed  Google Scholar 

  96. 96.

    Crowe S, Turpin SM, Ke F, Kemp BE, Watt MJ. Metabolic remodeling in adipocytes promotes ciliary neurotrophic factormediated fat loss in obesity. Endocrinology 2008; 149(5): 2546–2556

    Article  CAS  PubMed  Google Scholar 

  97. 97.

    Derouet D, Rousseau F, Alfonsi F, Froger J, Hermann J, Barbier F, Perret D, Diveu C, Guillet C, Preisser L, Dumont A, Barbado M, Morel A, de Lapeyriere O, Gascan H, Chevalier S. Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor. Proc Natl Acad Sci USA 2004; 101(14): 4827–4832

    Article  CAS  PubMed  Google Scholar 

  98. 98.

    Patidar M, Yadav N, Dalai SK. Interleukin 15: a key cytokine for immunotherapy. Cytokine Growth Factor Rev 2016; 31: 49–59

    Article  PubMed  Google Scholar 

  99. 99.

    Lacraz G, Rakotoarivelo V, Labbe SM, Vernier M, Noll C, Mayhue M, Stankova J, Schwertani A, Grenier G, Carpentier A, Richard D, Ferbeyre G, Fradette J, Rola-Pleszczynski M, Menendez A, Langlois MF, Ilangumaran S, Ramanathan S. Deficiency of interleukin-15 confers resistance to obesity by diminishing inflammation and enhancing the thermogenic function of adipose tissues. PLoS One 2016; 11(9): e0162995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Carbó N, Lopez-Soriano J, Costelli P, Alvarez B, Busquets S, Baccino FM, Quinn LS, Lopez-Soriano FJ, Argiles JM. Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control. Biochim Biophys Acta 2001; 1526(1): 17–24

    Article  PubMed  Google Scholar 

  101. 101.

    Barra NG, Reid S, MacKenzie R, Werstuck G, Trigatti BL, Richards C, Holloway AC, Ashkar AA. Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes. Obesity (Silver Spring) 2010; 18(8): 1601–1607

    Article  CAS  Google Scholar 

  102. 102.

    Barra NG, Chew MV, Reid S, Ashkar AA. Interleukin-15 treatment induces weight loss independent of lymphocytes. PLoS One 2012; 7(6): e39553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. 103.

    Neal JW, Clipstone NA. Calcineurin mediates the calciumdependent inhibition of adipocyte differentiation in 3T3-L1 cells. J Biol Chem 2002; 277(51): 49776–49781

    Article  CAS  PubMed  Google Scholar 

  104. 104.

    Pierce JR, Maples JM, Hickner RC. IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis. Am J Physiol Endocrinol Metab 2015; 308(12): E1131–E1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 1999; 17:701–738

    Article  CAS  PubMed  Google Scholar 

  106. 106.

    Walsh GM. Biologics targeting IL-5, IL-4 or IL-13 for the treatment of asthma—an update. Expert Rev Clin Immunol 2017; 13(2): 143–149

    Article  CAS  PubMed  Google Scholar 

  107. 107.

    Guenova E, Skabytska Y, Hoetzenecker W, Weindl G, Sauer K, Tham M, Kim KW, Park JH, Seo JH, Ignatova D, Cozzio A, Levesque MP, Volz T, Koberle M, Kaesler S, Thomas P, Mailhammer R, Ghoreschi K, Schakel K, Amarov B, Eichner M, Schaller M, Clark RA, Rocken M, Biedermann T. IL-4 abrogates T (H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells. Proc Natl Acad Sci USA 2015; 112(7): 2163–2168

    Article  CAS  PubMed  Google Scholar 

  108. 108.

    Huang XL, Wang YJ, Yan JW, Wan YN, Chen B, Li BZ, Yang GJ, Wang J. Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis. Inflamm Res 2015; 64(3–4): 151–159

    Article  CAS  PubMed  Google Scholar 

  109. 109.

    Johannsen DL, Tchoukalova Y, Tam CS, Covington JD, Xie W, Schwarz JM, Bajpeyi S, Ravussin E. Effect of 8 weeks of overfeeding on ectopic fat deposition and insulin sensitivity: testing the “adipose tissue expandability” hypothesis. Diabetes Care 2014; 37(10): 2789–2797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol 2009; 27:485–517

    Article  CAS  PubMed  Google Scholar 

  111. 111.

    Goswami J, Hernandez-Santos N, Zuniga LA, Gaffen SL. A boneprotective role for IL-17 receptor signaling in ovariectomy-induced bone loss. Eur J Immunol 2009; 39(10): 2831–2839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Shin JH, Shin DW, Noh M. Interleukin-17A inhibits adipocyte differentiation in human mesenchymal stem cells and regulates pro-inflammatory responses in adipocytes. Biochem Pharmacol 2009; 77(12): 1835–1844

    Article  CAS  PubMed  Google Scholar 

  113. 113.

    Capitini CM, Chisti AA, Mackall CL. Modulating T-cell homeostasis with IL-7: preclinical and clinical studies. J Intern Med 2009; 266(2): 141–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. 114.

    Maury E, Ehala-Aleksejev K, Guiot Y, Detry R, Vandenhooft A, Brichard SM. Adipokines oversecreted by omental adipose tissue in human obesity. Am J Physiol Endocrinol Metab 2007; 293(3): E656–E665

    Article  CAS  PubMed  Google Scholar 

  115. 115.

    Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D, Hollenbaugh D, Linnemann T, Qin M, Wong J, Chu K, Doberstein SK, Williams LT. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 2008; 320(5877): 807–811

    Article  CAS  PubMed  Google Scholar 

  116. 116.

    Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 2008; 8(7): 533–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Nakamichi Y, Udagawa N, Takahashi N. IL-34 and CSF-1: similarities and differences. J Bone Miner Metab 2013; 31(5): 486–495

    Article  CAS  PubMed  Google Scholar 

  118. 118.

    Parker BS, Rautela J, Hertzog PJ. Antitumour actions of interferons: implications for cancer therapy. Nat Rev Cancer 2016; 16(3): 131–144

    Article  CAS  PubMed  Google Scholar 

  119. 119.

    Hoffmann HH, Schneider WM, Rice CM. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol 2015; 36(3): 124–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    He B. Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ 2006; 13(3): 393–403

    Article  CAS  PubMed  Google Scholar 

  121. 121.

    Koivisto VA, Pelkonen R, Cantell K. Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes 1989; 38(5): 641–647

    Article  CAS  PubMed  Google Scholar 

  122. 122.

    O’Rourke RW, White AE, Metcalf MD, Winters BR, Diggs BS, Zhu X, Marks DL. Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice. Metabolism 2012; 61(8): 1152–1161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. 123.

    Keay S, Grossberg SE. Interferon inhibits the conversion of 3T3-L1 mouse fibroblasts into adipocytes. Proc Natl Acad Sci USA 1980; 77(7): 4099–4103

    Article  CAS  PubMed  Google Scholar 

  124. 124.

    McGillicuddy FC, Chiquoine EH, Hinkle CC, Kim RJ, Shah R, Roche HM, Smyth EM, Reilly MP. Interferon γ attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem 2009; 284(46): 31936–31944 doi:10.1074/jbc.M109.061655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. 125.

    Birk RZ, Rubinstein M. IFN-α induces apoptosis of adipose tissue cells. Biochem Biophys Res Commun 2006; 345(2): 669–674

    Article  CAS  PubMed  Google Scholar 

  126. 126.

    Panee J. Monocyte chemoattractant protein 1 (MCP-1) in obesity and diabetes. Cytokine 2012; 60(1): 1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. 127.

    Harman-Boehm I, Bluher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E, Shai I, Kloting N, Stumvoll M, Bashan N, Rudich A. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 2007; 92(6): 2240–2247

    Article  CAS  Google Scholar 

  128. 128.

    Famulla S, Horrighs A, Cramer A, Sell H, Eckel J. Hypoxia reduces the response of human adipocytes towards TNFα resulting in reduced NF-κB signaling and MCP-1 secretion. Int J Obes 2012; 36(7): 986–992

    Article  CAS  Google Scholar 

  129. 129.

    Aomatsu T, Imaeda H, Takahashi K, Fujimoto T, Kasumi E, Yoden A, Tamai H, Fujiyama Y, Andoh A. Tacrolimus (FK506) suppresses TNF-α-induced CCL2 (MCP-1) and CXCL10 (IP-10) expression via the inhibition of p38 MAP kinase activation in human colonic myofibroblasts. Int J Mol Med 2012; 30(5): 1152–1158

    Article  CAS  PubMed  Google Scholar 

  130. 130.

    Tateya S, Tamori Y, Kawaguchi T, Kanda H, Kasuga M. An increase in the circulating concentration of monocyte chemoattractant protein-1 elicits systemic insulin resistance irrespective of adipose tissue inflammation in mice. Endocrinology 2010; 151(3): 971–979

    Article  CAS  PubMed  Google Scholar 

  131. 131.

    Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AWJr. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006; 116(1): 115–124

    Article  CAS  Google Scholar 

  132. 132.

    Younce C, Kolattukudy P. MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy. Cell Physiol Biochem 2012; 30(2): 307–320

    Article  CAS  PubMed  Google Scholar 

  133. 133.

    Schmidt SF, Jorgensen M, Chen Y, Nielsen R, Sandelin A, Mandrup S. Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites. BMC Genomics 2011; 12:152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Mikkelsen TS, Xu Z, Zhang X, Wang L, Gimble JM, Lander ES, Rosen ED. Comparative epigenomic analysis of murine and human adipogenesis. Cell 2010; 143(1): 156–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. 135.

    Lindroos J, Husa J, Mitterer G, Haschemi A, Rauscher S, Haas R, Groger M, Loewe R, Kohrgruber N, Schrogendorfer KF, Prager G, Beck H, Pospisilik JA, Zeyda M, Stulnig TM, Patsch W, Wagner O, Esterbauer H, Bilban M. Human but not mouse adipogenesis is critically dependent on LMO3. Cell Metab 2013; 18(1): 62–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. 136.

    Abella V, Scotece M, Conde J, Pino J, Gonzalez-Gay MA, Gomez-Reino JJ, Mera A, Lago F, Gomez R, Gualillo O. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat Rev Rheumatol 2017; 13(2): 100–109

    Article  CAS  PubMed  Google Scholar 

  137. 137.

    Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395(6704): 763–770

    Article  CAS  PubMed  Google Scholar 

  138. 138.

    Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346(8): 570–578

    Article  CAS  PubMed  Google Scholar 

  139. 139.

    Behnes M, Brueckmann M, Lang S, Putensen C, Saur J, Borggrefe M, Hoffmann U. Alterations of leptin in the course of inflammation and severe sepsis. BMC Infect Dis 2012; 12:217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. 140.

    Fawcett RL, Waechter AS, Williams LB, Zhang P, Louie R, Jones R, Inman M, Huse J, Considine RV. Tumor necrosis factor-α inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans. J Clin Endocrinol Metab 2000; 85(2): 530–535

    CAS  PubMed  Google Scholar 

  141. 141.

    Granowitz EV. Transforming growth factor-β enhances and proinflammatory cytokines inhibit ob gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 1997; 240(2): 382–385

    Article  CAS  PubMed  Google Scholar 

  142. 142.

    Laharrague P, Truel N, Fontanilles AM, Corberand JX, Penicaud L, Casteilla L. Regulation by cytokines of leptin expression in human bone marrow adipocytes. Horm Metab Res 2000; 32(10): 381–385

    Article  CAS  PubMed  Google Scholar 

  143. 143.

    Gottschling-Zeller H, Birgel M, Scriba D, Blum WF, Hauner H. Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-α and transforming growth factor-β1. Eur J Endocrinol 1999; 141(4): 436–442 doi:10.1530/eje.0.1410436

    Article  CAS  PubMed  Google Scholar 

  144. 144.

    Grunfeld C, Zhao C, Fuller J, Pollack A, Moser A, Friedman J, Feingold KR. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest 1996; 97(9): 2152–2157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. 145.

    Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ3rd, Flier JS, Lowell BB, Fraker DL, Alexander HR. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 1997; 185(1): 171–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. 146.

    Padidar S, Farquharson AJ, Williams LM, Kelaiditi E, Hoggard N, Arthur JR, Drew JE. Leptin up-regulates pro-inflammatory cytokines in discrete cells within mouse colon. J Cell Physiol 2011; 226(8): 2123–2130

    Article  CAS  PubMed  Google Scholar 

  147. 147.

    Jitprasertwong P, Jaedicke KM, Nile CJ, Preshaw PM, Taylor JJ. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine 2014; 65(2): 222–230

    Article  CAS  PubMed  Google Scholar 

  148. 148.

    Tao C, Sifuentes A, Holland WL. Regulation of glucose and lipid homeostasis by adiponectin: effects on hepatocytes, pancreatic beta cells and adipocytes. Best Pract Res Clin Endocrinol Metab 2014; 28(1): 43–58

    Article  CAS  PubMed  Google Scholar 

  149. 149.

    Tilg H, Wolf AM. Adiponectin: a key fat-derived molecule regulating inflammation. Expert Opin Ther Targets 2005; 9(2): 245–251

    Article  CAS  PubMed  Google Scholar 

  150. 150.

    Robinson K, Prins J, Venkatesh B. Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care 2011; 15(2): 221

    Article  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002; 8(7): 731–737

    Article  CAS  PubMed  Google Scholar 

  152. 152.

    Jiang CY, Wang W, Tang JX, Yuan ZR. The adipocytokine resistin stimulates the production of proinflammatory cytokines TNF-α and IL-6 in pancreatic acinar cells via NF-κB activation. J Endocrinol Invest 2013; 36(11): 986–992

    CAS  PubMed  Google Scholar 

  153. 153.

    Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P. Dynamics of fat cell turnover in humans. Nature 2008; 453(7196): 783–787

    Article  CAS  PubMed  Google Scholar 

  154. 154.

    Samocha-Bonet D, Chisholm DJ, Tonks K, Campbell LV, Greenfield JR. Insulin-sensitive obesity in humans — a ‘favorable fat’ phenotype? Trends Endocrinol Metab 2012; 23(3): 116–124

    Article  CAS  PubMed  Google Scholar 

  155. 155.

    Tchkonia T, Thomou T, Zhu Y, Karagiannides I, Pothoulakis C, Jensen MD, Kirkland JL. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17(5): 644–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. 156.

    Joe AW, Yi L, Even Y, Vogl AW, Rossi FM. Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet. Stem Cells 2009; 27(10): 2563–2570

    Article  CAS  PubMed  Google Scholar 

  157. 157.

    van Beek L, van Klinken JB, Pronk AC, van Dam AD, Dirven E, Rensen PC, Koning F, Willems van Dijk K, van Harmelen V. The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice. Diabetologia 2015; 58(7): 1601–1609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. 158.

    Gustafson B, Hedjazifar S, Gogg S, Hammarstedt A, Smith U. Insulin resistance and impaired adipogenesis. Trends Endocrinol Metab 2015; 26(4): 193–200

    Article  CAS  PubMed  Google Scholar 

  159. 159.

    Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW2nd, DeFuria J, Jick Z, Greenberg AS, Obin MS. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 2007; 56(12): 2910–2918

    Article  CAS  PubMed  Google Scholar 

  160. 160.

    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. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 2009; 29(16): 4467–4483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. 161.

    Kim S, Joe Y, Jeong SO, Zheng M, Back SH, Park SW, Ryter SW, Chung HT. Endoplasmic reticulum stress is sufficient for the induction of IL-1β production via activation of the NF-κB and inflammasome pathways. Innate Immun 2014; 20(8): 799–815

    Article  CAS  PubMed  Google Scholar 

  162. 162.

    Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 2011; 17(2): 179–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. 163.

    Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 2011; 12(5): 408–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Wernstedt Asterholm I, Tao C, Morley TS, Wang QA, Delgado-Lopez F, Wang ZV, Scherer PE. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab 2014; 20(1): 103–118

    Article  CAS  Google Scholar 

  165. 165.

    Dali-Youcef N, Mecili M, Ricci R, Andres E. Metabolic inflammation: connecting obesity and insulin resistance. Ann Med 2013; 45(3): 242–253

    Article  CAS  PubMed  Google Scholar 

  166. 166.

    Tchoukalova Y, Koutsari C, Jensen M. Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 2007; 50(1): 151–157

    Article  CAS  PubMed  Google Scholar 

  167. 167.

    Adiels M, Westerbacka J, Soro-Paavonen A, Hakkinen AM, Vehkavaara S, Caslake MJ, Packard C, Olofsson SO, Yki-Jarvinen H, Taskinen MR, Boren J. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. Diabetologia 2007; 50(11): 2356–2365

    Article  CAS  PubMed  Google Scholar 

  168. 168.

    Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444(7121): 881–887

    Article  CAS  PubMed  Google Scholar 

  169. 169.

    Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 2012; 308(11): 1150–1159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. 170.

    Shuster A, Patlas M, Pinthus JH, Mourtzakis M. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol 2012; 85(1009): 1–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. 171.

    Smith U. Abdominal obesity: a marker of ectopic fat accumulation. J Clin Invest 2015; 125(5): 1790–1792

    Article  PubMed  PubMed Central  Google Scholar 

  172. 172.

    Pellegrinelli V, Carobbio S, Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 2016; 59(6): 1075–1088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. 173.

    Wang Y, Wang H, Hegde V, Dubuisson O, Gao Z, Dhurandhar NV, Ye J. Interplay of pro- and anti-inflammatory cytokines to determine lipid accretion in adipocytes. Int J Obes 2013; 37(11): 1490–1498

    Article  CAS  Google Scholar 

  174. 174.

    Kiortsis DN, Mavridis AK, Vasakos S, Nikas SN, Drosos AA. Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis 2005; 64(5): 765–766

    Article  CAS  PubMed  Google Scholar 

  175. 175.

    Huvers FC, Popa C, Netea MG, van den Hoogen FH, Tack CJ. Improved insulin sensitivity by anti-TNFα antibody treatment in patients with rheumatic diseases. Ann Rheum Dis 2007; 66(4): 558–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. 176.

    Marra M, Campanati A, Testa R, Sirolla C, Bonfigli AR, Franceschi C, Marchegiani F, Offidani A. Effect of etanercept on insulin sensitivity in nine patients with psoriasis. Int J Immunopathol Pharmacol 2007; 20(4): 731–736

    Article  CAS  PubMed  Google Scholar 

  177. 177.

    Solomon DH, Massarotti E, Garg R, Liu J, Canning C, Schneeweiss S. Association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis. JAMA 2011; 305(24): 2525–2531

    Article  CAS  PubMed  Google Scholar 

  178. 178.

    Parmentier-Decrucq E, Duhamel A, Ernst O, Fermont C, Louvet A, Vernier-Massouille G, Cortot A, Colombel JF, Desreumaux P, Peyrin-Biroulet L. Effects of infliximab therapy on abdominal fat and metabolic profile in patients with Crohn’s disease. Inflamm Bowel Dis 2009; 15(10): 1476–1484

    Article  PubMed  Google Scholar 

  179. 179.

    O’Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev 2008; 226: 10–18

    Article  PubMed  Google Scholar 

  180. 180.

    Stienstra R, Joosten LA, Koenen T, van Tits B, van Diepen JA, van den Berg SA, Rensen PC, Voshol PJ, Fantuzzi G, Hijmans A, Kersten S, Muller M, van den Berg WB, van Rooijen N, Wabitsch M, Kullberg BJ, van der Meer JW, Kanneganti T, Tack CJ, Netea MG. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab 2010; 12(6): 593–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. 181.

    Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov 2014; 13(6): 465–476

    Article  CAS  PubMed  Google Scholar 

  182. 182.

    Gabay C, McInnes IB, Kavanaugh A, Tuckwell K, Klearman M, Pulley J, Sattar N. Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis. Ann Rheum Dis 2016; 75(10): 1806–1812

    Article  CAS  PubMed  Google Scholar 

  183. 183.

    Laakso M, Kuusisto J. Insulin resistance and hyperglycaemia in cardiovascular disease development. Nat Rev Endocrinol 2014; 10(5): 293–302

    Article  CAS  PubMed  Google Scholar 

  184. 184.

    Wang M, Gao M, Liao J, Qi Y, Du X, Wang Y, Li L, Liu G, Yang H. Adipose tissue deficiency results in severe hyperlipidemia and atherosclerosis in the low-density lipoprotein receptor knockout mice. Biochim Biophys Acta 2016; 1861(5): 410–418

    Article  CAS  PubMed  Google Scholar 

  185. 185.

    Fox CS, Coady S, Sorlie PD,D’ Agostino RBSr, Pencina MJ, Vasan RS, Meigs JB, Levy D, Savage PJ. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation 2007; 115(12): 1544–1550

    Article  PubMed  Google Scholar 

  186. 186.

    Loomba R, Abraham M, Unalp A, Wilson L, Lavine J, Doo E, Bass NM. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 2012; 56(3): 943–951

    Article  PubMed  PubMed Central  Google Scholar 

  187. 187.

    Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middleaged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011; 140(1): 124–131

    Article  Google Scholar 

  188. 188.

    Betteridge DJ, Carmena R. The diabetogenic action of statins — mechanisms and clinical implications. Nat Rev Endocrinol 2016; 12(2): 99–110

    Article  CAS  PubMed  Google Scholar 

  189. 189.

    Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SCJr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SCJr, Tomaselli GF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(25 Suppl 2): S1–S45

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (Nos. 81622008 and 81470579) (to Jing Wang).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jing Wang.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jiang, N., Li, Y., Shu, T. et al. Cytokines and inflammation in adipogenesis: an updated review. Front. Med. 13, 314–329 (2019). https://doi.org/10.1007/s11684-018-0625-0

Download citation

Keywords

  • cytokines
  • inflammation
  • adipogenesis
  • type 2 diabetes mellitus
  • metabolic disorder