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Journal of Obesity
Volume 2013 (2013), Article ID 616193, 9 pages
http://dx.doi.org/10.1155/2013/616193
Review Article

The Role of the Immune System in Obesity and Insulin Resistance

1Diabetes Research Center, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX 77030, USA
2Endocrine Service, Ben Taub General Hospital, Houston, TX 77030, USA

Received 29 November 2012; Accepted 20 February 2013

Academic Editor: Nicola Abate

Copyright © 2013 Payal S. Patel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. M. Flegal, M. D. Carroll, C. L. Ogden, and C. L. Johnson, “Prevalence and trends in obesity among US adults, 1999-2000,” Journal of the American Medical Association, vol. 288, no. 14, pp. 1723–1727, 2002. View at Scopus
  2. H. Xu, G. T. Barnes, Q. Yang et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1821–1830, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante, “Obesity is associated with macrophage accumulation in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. M. M. Altintas, A. Azad, B. Nayer et al., “Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice,” Journal of Lipid Research, vol. 52, no. 3, pp. 480–488, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Cancello, J. Tordjman, C. Poitou et al., “Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity,” Diabetes, vol. 55, no. 6, pp. 1554–1561, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Kolak, J. Westerbacka, V. R. Velagapudi et al., “Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity,” Diabetes, vol. 56, no. 8, pp. 1960–1968, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Gastaldelli, Y. Miyazaki, M. Pettiti et al., “Metabolic effects of visceral fat accumulation in type 2 diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 11, pp. 5098–5103, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Kosteli, E. Sugaru, G. Haemmerle et al., “Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue,” Journal of Clinical Investigation, vol. 120, no. 10, pp. 3466–3479, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. J. M. Olefsky and C. K. Glass, “Macrophages, inflammation, and insulin resistance,” Annual Review of Physiology, vol. 72, pp. 219–246, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. P. Wang, E. Mariman, J. Renes, and J. Keijer, “The secretory function of adipocytes in the physiology of white adipose tissue,” Journal of Cellular Physiology, vol. 216, no. 1, pp. 3–13, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. S. P. Weisberg, D. Hunter, R. Huber et al., “CCR2 modulates inflammatory and metabolic effects of high-fat feeding,” Journal of Clinical Investigation, vol. 116, no. 1, pp. 115–124, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. D. Y. Oh, H. Morinaga, S. Talukdar, et al., “Increased macrophage migration into adipose tissue in obese mice,” Diabetes, vol. 61, no. 2, pp. 346–354, 2012. View at Publisher · View at Google Scholar
  13. H. Kanda, S. Tateya, Y. Tamori et al., “MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity,” Journal of Clinical Investigation, vol. 116, no. 6, pp. 1494–1505, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. C. C. Féral, J. G. Neels, C. Kummer, M. Slepak, J. M. Olefsky, and M. H. Ginsberg, “Blockade of α4 integrin signaling ameliorates the metabolic consequences of high-fat diet-induced obesity,” Diabetes, vol. 57, no. 7, pp. 1842–1851, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Chang, S. H. Chiang, and A. R. Saltiel, “Insulin signaling and the regulation of glucose transport,” Molecular Medicine, vol. 10, no. 7–12, pp. 65–71, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. L. A. Lesniewski, S. E. Hosch, J. G. Neels et al., “Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance,” Nature Medicine, vol. 13, no. 4, pp. 455–462, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. S. K. Chakrabarti, Y. Wen, A. D. Dobrian et al., “Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats,” American Journal of Physiology, vol. 300, no. 1, pp. E175–E187, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Spite, J. Hellmann, Y. Tang, et al., “Deficiency of the leukotriene B4 receptor, BLT-1 protects against systemic insulin resistance in diet-induced obesity,” The Journal of Immunology, vol. 187, no. 4, pp. 1942–1949, 2011. View at Publisher · View at Google Scholar
  19. H. Kitade, K. Sawamoto, M. Nagashimada, et al., “CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status,” Diabetes, vol. 61, no. 7, pp. 1680–1690, 2012. View at Publisher · View at Google Scholar
  20. S. Goerdt, O. Politz, K. Schledzewski et al., “Alternative versus classical activation of macrophages,” Pathobiology, vol. 67, no. 5-6, pp. 222–226, 2000. View at Scopus
  21. S. Gordon, “Alternative activation of macrophages,” Nature Reviews Immunology, vol. 3, no. 1, pp. 23–35, 2003. View at Publisher · View at Google Scholar
  22. C. N. Lumeng, J. L. Bodzin, and A. R. Saltiel, “Obesity induces a phenotypic switch in adipose tissue macrophage polarization,” Journal of Clinical Investigation, vol. 117, no. 1, pp. 175–184, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. C. N. Lumeng, J. B. Delproposto, D. J. Westcott, and A. R. Saltiel, “Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes,” Diabetes, vol. 57, no. 12, pp. 3239–3246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. C. N. Lumeng, S. M. DeYoung, J. L. Bodzin, and A. R. Saltiel, “Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity,” Diabetes, vol. 56, no. 1, pp. 16–23, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. M. T. A. Nguyen, S. Favelyukis, A. K. Nguyen et al., “A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via toll-like receptors 2 and 4 and JNK-dependent pathways,” Journal of Biological Chemistry, vol. 282, no. 48, pp. 35279–35292, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Patsouris, P. P. Li, D. Thapar, J. Chapman, J. M. Olefsky, and J. G. Neels, “Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals,” Cell Metabolism, vol. 8, no. 4, pp. 301–309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. P. Li, M. Lu, M. T. Nguyen, et al., “Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice,” The Journal of Biological Chemistry, vol. 285, no. 20, pp. 15333–15345, 2010. View at Publisher · View at Google Scholar
  28. S. Fujisaka, I. Usui, A. Bukhari et al., “Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice,” Diabetes, vol. 58, no. 11, pp. 2574–2582, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. M. E. Shaul, G. Bennett, K. J. Strissel, A. S. Greenberg, and M. S. Obin, “Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet—induced obesity in mice,” Diabetes, vol. 59, no. 5, pp. 1171–1181, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. K. J. Strissel, Z. Stancheva, H. Miyoshi et al., “Adipocyte death, adipose tissue remodeling, and obesity complications,” Diabetes, vol. 56, no. 12, pp. 2910–2918, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. B. Kabon, A. Nagele, D. Reddy et al., “Obesity decreases perioperative tissue oxygenation,” Anesthesiology, vol. 100, no. 2, pp. 274–280, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Jantsch, D. Chakravortty, N. Turza et al., “Hypoxia and hypoxia-inducible factor-1α modulate lipopolysaccharide-induced dendritic cell activation and function,” Journal of Immunology, vol. 180, no. 7, pp. 4697–4705, 2008. View at Scopus
  33. C. Jiang, A. Qu, T. Matsubara, et al., “Disruption of hypoxia-inducible factor 1 in adipocytes improves insulin sensitivity and decreases adiposity in high-fat diet-fed mice,” Diabetes, vol. 60, no. 10, pp. 2484–2495, 2011. View at Publisher · View at Google Scholar
  34. A. S. Greenberg, J. J. Egan, S. A. Wek, N. B. Garty, E. J. Blanchette-Mackie, and C. Londos, “Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets,” Journal of Biological Chemistry, vol. 266, no. 17, pp. 11341–11346, 1991. View at Scopus
  35. S. Cinti, G. Mitchell, G. Barbatelli et al., “Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans,” Journal of Lipid Research, vol. 46, no. 11, pp. 2347–2355, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. I. Murano, G. Barbatelli, V. Parisani et al., “Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice,” Journal of Lipid Research, vol. 49, no. 7, pp. 1562–1568, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. C. M. Apovian, S. Bigornia, M. Mott et al., “Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 9, pp. 1654–1659, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. G. S. Hotamisligil, P. Arner, J. F. Caro, R. L. Atkinson, and B. M. Spiegelman, “Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance,” Journal of Clinical Investigation, vol. 95, no. 5, pp. 2409–2415, 1995. View at Scopus
  39. Z. Gao, J. Hwang, F. Bataille, et al., “Serine phosphorylation of insulin receptor substrate 1 by inhibitor κB kinase complex,” The Journal of Biological Chemistry, vol. 277, no. 50, pp. 48115–48121, 2002. View at Publisher · View at Google Scholar
  40. J. Hirosumi, G. Tuncman, L. Chang, et al., “A central role for JNK in obesity and insulin resistance,” Nature, vol. 420, no. 6913, pp. 333–336, 2002. View at Publisher · View at Google Scholar
  41. S. Vallabhapurapu and M. Karin, “Regulation and function of NF-κB transcription factors in the immune system,” Annual Review of Immunology, vol. 27, pp. 693–733, 2009. View at Publisher · View at Google Scholar
  42. M. C. Arkan, A. L. Hevener, F. R. Greten et al., “IKK-β links inflammation to obesity-induced insulin resistance,” Nature Medicine, vol. 11, no. 2, pp. 191–198, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. G. Solinas and M. Karin, “JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction,” FASEB Journal, vol. 24, no. 8, pp. 2596–2611, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Solinas, C. Vilcu, J. G. Neels et al., “JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity,” Cell Metabolism, vol. 6, no. 5, pp. 386–397, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. J. Y. Lee, K. H. Sohn, S. H. Rhee, and D. Hwang, “Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through toll-like receptor 4,” Journal of Biological Chemistry, vol. 276, no. 20, pp. 16683–16689, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. D. M. L. Tsukumo, M. A. Carvalho-Filho, J. B. C. Carvalheira et al., “Loss-of-function mutation in toll-like receptor 4 prevents diet-induced obesity and insulin resistance,” Diabetes, vol. 56, no. 8, pp. 1986–1998, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. S. K. Koliwad, R. S. Streeper, M. Monetti et al., “DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation,” Journal of Clinical Investigation, vol. 120, no. 3, pp. 756–767, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. B. Vandanmagsar, Y. H. Youm, A. Ravussin et al., “The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance,” Nature Medicine, vol. 17, no. 2, pp. 179–189, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. A. R. Saltiel, “Fishing out a sensor for anti-inflammatory oils,” Cell, vol. 142, no. 5, pp. 672–674, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Hummasti and G. S. Hotamisligil, “Endoplasmic reticulum stress and inflammation in obesity and diabetes,” Circulation Research, vol. 107, no. 5, pp. 579–591, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. V. Bocher, G. Chinetti, J. C. Fruchart, and B. Staels, “Role of the peroxisome proliferator-activated receptors (PPARS) in the regulation of lipids and inflammation control,” Journal de la Societe de Biologie, vol. 196, no. 1, pp. 47–52, 2002. View at Scopus
  52. A. L. Hevener, J. M. Olefsky, D. Reichart et al., “Macrophage PPARγ is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones,” Journal of Clinical Investigation, vol. 117, no. 6, pp. 1658–1669, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Kang, S. M. Reilly, V. Karabacak et al., “Adipocyte-derived Th2 cytokines and myeloid PPARδ regulate macrophage polarization and insulin sensitivity,” Cell Metabolism, vol. 7, no. 6, pp. 485–495, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Feuerer, L. Herrero, D. Cipolletta et al., “Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters,” Nature Medicine, vol. 15, no. 8, pp. 930–939, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Nishimura, I. Manabe, M. Nagasaki et al., “CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity,” Nature Medicine, vol. 15, no. 8, pp. 914–920, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Winer, Y. Chan, G. Paltser et al., “Normalization of obesity-associated insulin resistance through immunotherapy,” Nature Medicine, vol. 15, no. 8, pp. 921–929, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. D. A. Winer, S. Winer, L. Shen et al., “B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies,” Nature Medicine, vol. 17, no. 5, pp. 610–617, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Liu, A. Divoux, J. Sun et al., “Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice,” Nature Medicine, vol. 15, no. 8, pp. 940–945, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Wu, A. B. Molofsky, H. E. Liang et al., “Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis,” Science, vol. 332, no. 6026, pp. 243–247, 2011. View at Publisher · View at Google Scholar · View at Scopus