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Journal of Obesity
Volume 2013 (2013), Article ID 616193, 9 pages
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- J. M. Olefsky and C. K. Glass, “Macrophages, inflammation, and insulin resistance,” Annual Review of Physiology, vol. 72, pp. 219–246, 2009.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- S. Goerdt, O. Politz, K. Schledzewski et al., “Alternative versus classical activation of macrophages,” Pathobiology, vol. 67, no. 5-6, pp. 222–226, 2000.
- S. Gordon, “Alternative activation of macrophages,” Nature Reviews Immunology, vol. 3, no. 1, pp. 23–35, 2003.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- B. Kabon, A. Nagele, D. Reddy et al., “Obesity decreases perioperative tissue oxygenation,” Anesthesiology, vol. 100, no. 2, pp. 274–280, 2004.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- A. R. Saltiel, “Fishing out a sensor for anti-inflammatory oils,” Cell, vol. 142, no. 5, pp. 672–674, 2010.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.