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Adipose Tissue Inflammation in the Pathogenesis of Type 2 Diabetes

  • Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
  • Published:
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Abstract

At least 2.8 million people die each year as a result of being overweight or obese, and the biggest burden being obesity-related diseases. Overweight and obesity account for a major proportion of type 2 diabetes (T2D) cases. Obesity is associated with inflammation in adipose tissue, namely an infiltration and expansion of macrophages, which produce inflammatory cytokines that interfere with insulin signaling, and a loss of protective cells that promote adipose homeostasis. Thus, it is now clear that inflammation is an underlying cause or contributor to T2D as well as many other obesity-induced diseases, including atherosclerosis and cancer. Inflammatory pathways contribute to impaired glucose handling by adipocytes, hepatocytes, and muscle cells and interfere with insulin production and insulin signaling. This review highlights the roles of the different immune populations in lean adipose tissue and their importance in tissue homeostasis to keep inflammation at bay. We also discuss the changes that occur in these immune cells during the development of obesity, which has detrimental effects on the health of adipose tissue, and local and systemic insulin resistance.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ranvier L. Du dévelopment et de l’accroisement des vaisseux sanguins. Arch Physiol. 1874;1:429–50.

    Google Scholar 

  2. Platell C et al. The omentum. World J Gastroenterol. 2000;6(2):169–76.

    PubMed  PubMed Central  Google Scholar 

  3. Zhang LJ et al. Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science. 2015;347(6217):67–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Uysal KT et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389(6651):610–4.

    Article  CAS  PubMed  Google Scholar 

  6. Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol. 2012;13(8):707–12.

    Article  CAS  PubMed  Google Scholar 

  7. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Lynch L. Adipose invariant natural killer T cells. Immunology. 2014;142(3):337–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Wu D et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332(6026):243–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Feuerer M et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kazuyo Moro TY, Tanabe M, Takeuch T, Ikawa T, Hiroshi Kawamoto J-IF, Ohtani M, et al. Innate production of TH2 cytokines by adipose tissue-associated c-Kit1Sca-11 lymphoid cells. Nature. 2010;463:540–6.

    Article  PubMed  CAS  Google Scholar 

  12. Molofsky AB et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013;210(3):535–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Brestoff JR, Artis D. Immune regulation of metabolic homeostasis in health and disease. Cell. 2015;161(1):146–60.

    Article  CAS  PubMed  Google Scholar 

  14. Elgazar-Carmon V et al. Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res. 2008;49(9):1894–903.

    Article  CAS  PubMed  Google Scholar 

  15. Weisberg SP et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Amano SU et al. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab. 2014;19(1):162–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Lynch L et al. Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity. Eur J Immunol. 2009;39(7):1893–901.

    Article  CAS  PubMed  Google Scholar 

  18. Lynch L et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity. 2012;37(3):574–87.

    Article  CAS  PubMed  Google Scholar 

  19. Halberg N et al. Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol. 2009;29(16):4467–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Unger RH, Scherer PE. Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab. 2010;21(6):345–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Ozcan U et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306(5695):457–61.

    Article  PubMed  CAS  Google Scholar 

  22. Shi H et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116(11):3015–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Exley M et al. The interplay between the immune system and adipose in obesity. J Endocrinol. 2014;223:R41–8.

    Article  CAS  PubMed  Google Scholar 

  24. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121(6):2094–101.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Odegaard JI et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007;447(7148):1116–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Lee YS et al. Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes. 2011;60(10):2474–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Patsouris D et al. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 2008;8(4):301–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Kosteli A et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest. 2010;120(10):3466–79.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Wentworth JM et al. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes. 2010;59(7):1648–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Han MS et al. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science. 2013;339(6116):218–22.

    Article  CAS  PubMed  Google Scholar 

  31. Brigl M, Brenner MB. CD1: antigen presentation and T cell function. Annu Rev Immunol. 2004;22:817–90.

    Article  CAS  PubMed  Google Scholar 

  32. Beckman EM et al. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature. 1994;372(6507):691–4.

    Article  CAS  PubMed  Google Scholar 

  33. Lydia Lynch XM, Zhang S, Brennan PJ, Moseman A, Lester C, Besra G, et al. Regulatory iNKT cells lack PLZF expression and control Treg cell and macrophage homeostasis in adipose tissue. Nat Immunol. 2014;16:85–95.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Schipper HS et al. Natural killer T cells in adipose tissue prevent insulin resistance. J Clin Invest. 2012;122(9):3343–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Ji Y et al. Activation of natural killer T cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity. J Biol Chem. 2012;287(17):13561–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Huh JY et al. A novel function of adipocytes in lipid antigen presentation to iNKT cells. Mol Cell Biol. 2013;33(2):328–39.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Wu L et al. Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice. Proc Natl Acad Sci U S A. 2012;109(19):E1143–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Mantell BS et al. Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS One. 2011;6(6):e19831.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Nicholson JK et al. Host-gut microbiota metabolic interactions. Science. 2012;336(6086):1262–7.

    Article  CAS  PubMed  Google Scholar 

  40. Hams E et al. Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice. J Immunol. 2013;191(11):5349–53.

    Article  CAS  PubMed  Google Scholar 

  41. Kjer-Nielsen L et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012;491(7426):717–23. This study, for the first time, identified the elusive antigen for MAIT cells, and knowing that MAIT cells may play a role in obesity, it will be fascinating to see if obesity induces alterations in vitamin metabolites which then affects the immune system.

    CAS  PubMed  Google Scholar 

  42. Patel O et al. Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Nat Commun. 2013;4:2142.

    PubMed  Google Scholar 

  43. Carolan E et al. Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity. J Immunol. 2015;194(12):5775–80.

    Article  CAS  PubMed  Google Scholar 

  44. Magalhaes I et al. Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients. J Clin Invest. 2015;125(4):1752–62.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Zuniga LA et al. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol. 2010;185(11):6947–59.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Lee MW et al. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell. 2015;160(1–2):74–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Brestoff JR et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature. 2015;519(7542):242–6. This elegant study shows how innate immune cells directly regulate metabolism and body weight through their production of methionine-enkephalin peptides.

    Article  CAS  PubMed  Google Scholar 

  48. Benoist C, Mathis D. Treg cells, life history, and diversity. Cold Spring Harb Perspect Biol. 2012;4(9):a007021.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Kolodin D et al. Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice. Cell Metab. 2015;21(4):543–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vasanthakumar A et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol. 2015;16(3):276–85. This study highlights how immune cells in adipose tissue may be specially adapted to their environment, due to the cytokine milieu, which then controls their regulatory function which is critical for adipose homeostasis.

    Article  CAS  PubMed  Google Scholar 

  51. Cipolletta D et al. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature. 2012;486(7404):549–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol. 2010;11(1):34–46.

    Article  PubMed  CAS  Google Scholar 

  53. Shen L et al. B-1a lymphocytes attenuate insulin resistance. Diabetes. 2015;64(2):593–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Nishimura S et al. Adipose natural regulatory B cells negatively control adipose tissue inflammation. Cell Metab. 2013. doi:10.1016/j.cmet.2013.09.017.

    Google Scholar 

  55. Winer DA et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17(5):610–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Yamaguchi Y et al. Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor. J Exp Med. 1988;167(5):1737–42.

    Article  CAS  PubMed  Google Scholar 

  57. Yu C. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med. 2002;195(11):1387–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Qiu Y et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell. 2014;157(6):1292–308.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Rao RR et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014;157(6):1279–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Hashiguchi M et al. IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells. Eur J Immunol. 2015;45(3):876–85.

    Article  CAS  PubMed  Google Scholar 

  62. Nishimura S et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914–20.

    Article  CAS  PubMed  Google Scholar 

  63. Rausch ME et al. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond). 2008;32(3):451–63.

    Article  CAS  Google Scholar 

  64. Sun B, Zhang Y. Overview of orchestration of CD4+ T cell subsets in immune responses. Adv Exp Med Biol. 2014;841:1–13.

    Article  PubMed  Google Scholar 

  65. Cho KW et al. An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation. Cell Rep. 2014;9(2):605–17.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Bertola A et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes. 2012;61(9):2238–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Fabbrini E et al. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013;145(2):366-74 e1–3.

    Article  CAS  Google Scholar 

  68. Winer S et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15(8):921–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Stolarczyk E et al. Improved insulin sensitivity despite increased visceral adiposity in mice deficient for the immune cell transcription factor T-bet. Cell Metab. 2013;17(4):520–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Dalmas E et al. T cell-derived IL-22 amplifies IL-1beta-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes. Diabetes. 2014;63(6):1966–77.

    Article  CAS  PubMed  Google Scholar 

  71. Moraes-Vieira PM et al. RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell Metab. 2014;19(3):512–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Talukdar S et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med. 2012;18(9):1407–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Liu J et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med. 2009;15(8):940–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Zhang J, Shi GP. Mast cells and metabolic syndrome. Biochim Biophys Acta. 2012;1822(1):14–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Poglio S et al. Adipose tissue as a dedicated reservoir of functional mast cell progenitors. Stem Cells. 2010;28(11):2065–72.

    Article  CAS  PubMed  Google Scholar 

  76. Wang J, Shi GP. Mast cell stabilization: novel medication for obesity and diabetes. Diabetes Metab Res Rev. 2011;27(8):919–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Geneva WHO. Global status report on noncommunicable diseases 2014, 2012.

  78. Ursini F, Naty S, Grembiale RD. Infliximab and insulin resistance. Autoimmun Rev. 2010;9(8):536–9.

    Article  CAS  PubMed  Google Scholar 

  79. Dominguez H et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res. 2005;42(6):517–25.

    Article  CAS  PubMed  Google Scholar 

  80. Ofei F et al. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes. 1996;45(7):881–5.

    Article  PubMed  Google Scholar 

  81. Stanley TL et al. TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J Clin Endocrinol Metab. 2011;96(1):E146–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095–147.

    CAS  PubMed  Google Scholar 

  83. Vandanmagsar B et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–88.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Masters SL et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol. 2010;11(10):897–904.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Boni-Schnetzler M et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab. 2008;93(10):4065–74.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Ehses JA et al. IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Natl Acad Sci U S A. 2009;106(33):13998–4003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Owyang AM et al. XOMA 052, an anti-IL-1{beta} monoclonal antibody, improves glucose control and {beta}-cell function in the diet-induced obesity mouse model. Endocrinology. 2010;151(6):2515–27.

    Article  CAS  PubMed  Google Scholar 

  88. Larsen CM et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356(15):1517–26.

    Article  CAS  PubMed  Google Scholar 

  89. Rissanen A et al. Effect of anti-IL-1beta antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab. 2012;14(12):1088–96.

    Article  CAS  PubMed  Google Scholar 

  90. Sloan-Lancaster J et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care. 2013;36(8):2239–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Williamson RT. On the treatment of glycosuria and diabetes mellitus with sodium salicylate. Br Med J. 1901;1(2100):760–2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Goldfine AB et al. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008;1(1):36–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014;13(6):465–76.

    Article  CAS  PubMed  Google Scholar 

  94. Yuan M et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. 2001;293(5535):1673–7.

    Article  CAS  PubMed  Google Scholar 

  95. Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 1998;396(6706):77–80.

    Article  CAS  PubMed  Google Scholar 

  96. Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 1994;265(5174):956–9.

    Article  CAS  PubMed  Google Scholar 

  97. Fleischman A et al. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31(2):289–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Goldfine AB et al. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2010;152(6):346–57.

    Article  PubMed Central  PubMed  Google Scholar 

  99. Goldfine AB et al. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2013;159(1):1–12.

    Article  PubMed Central  PubMed  Google Scholar 

  100. Obstfeld AE et al. C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis. Diabetes. 2010;59(4):916–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Piemonti L et al. Association between plasma monocyte chemoattractant protein-1 concentration and cardiovascular disease mortality in middle-aged diabetic and nondiabetic individuals. Diabetes Care. 2009;32(11):2105–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Simeoni E et al. Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and type 2 diabetes mellitus. Diabetologia. 2004;47(9):1574–80.

    Article  CAS  PubMed  Google Scholar 

  103. Jing Y et al. Monocyte chemoattractant protein 1–2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population. Clin Chim Acta. 2011;412(5–6):466–9.

    Article  CAS  PubMed  Google Scholar 

  104. Zietz B et al. Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the −2518 A–>G promoter polymorphism. Diabetes Obes Metab. 2005;7(5):570–8.

    Article  CAS  PubMed  Google Scholar 

  105. Lloyd CM et al. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J Exp Med. 1997;185(7):1371–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Haringman JJ et al. A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(8):2387–92.

    Article  CAS  PubMed  Google Scholar 

  107. Bruhl H et al. Dual role of CCR2 during initiation and progression of collagen-induced arthritis: evidence for regulatory activity of CCR2+ T cells. J Immunol. 2004;172(2):890–8.

    Article  PubMed  Google Scholar 

  108. Brodmerkel CM et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005;175(8):5370–8.

    Article  CAS  PubMed  Google Scholar 

  109. Horvath C et al. Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates: inhibitory potential depends on type of injury and leukocytes targeted. Circ Res. 2002;90(4):488–94.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Cancello R et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes. 2005;54(8):2277–86.

    Article  CAS  PubMed  Google Scholar 

  112. Troseid M et al. Exercise reduces plasma levels of the chemokines MCP-1 and IL-8 in subjects with the metabolic syndrome. Eur Heart J. 2004;25(4):349–55.

    Article  CAS  PubMed  Google Scholar 

  113. Tateya S et al. 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):971–9.

    Article  CAS  PubMed  Google Scholar 

  114. Hanefeld M, Schell E, Gouni-Berthold I, Melichar M, Vesela I, Johnson D, et al. Orally-administered chemokine receptor CCR2 antagonist CCX140-B in type 2 diabetes: a pilot double-blind, randomized clinical trial. J Diabetes Metab. 2012;3(9):1–8.

    Article  CAS  Google Scholar 

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Ayano Kohlgruber and Lydia Lynch declare that they have no conflict of interest.

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  1. Division of Rheumatology, Immunology and Allergy, Department of Medicine Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Ayano Kohlgruber & Lydia Lynch

  2. Division of Endocrinology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Lydia Lynch

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  1. Ayano Kohlgruber
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Correspondence to Lydia Lynch.

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This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance

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Kohlgruber, A., Lynch, L. Adipose Tissue Inflammation in the Pathogenesis of Type 2 Diabetes. Curr Diab Rep 15, 92 (2015). https://doi.org/10.1007/s11892-015-0670-x

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