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Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

  • Orla M. Finucane (a1) (a2), Clare M. Reynolds (a2), Fiona C. McGillicuddy (a2) and Helen M. Roche (a2)

Abstract

High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

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Corresponding author

* Corresponding author: Professor Helen M. Roche, fax +353 1 716 7601, email Helen.roche@ucd.ie

References

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1. Flegal, KM, Graubard, BI, Williamson, DF et al. (2007) Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 298, 20282037.
2. The World Health Organisation (2011) Obesity and overweight. Available at: http://www.who.int./mediacentre/factsheet/fs311/en/.
3. Finucane, MM, Stevens, GA, Cowan, MJ et al. (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 377, 557567.
4. Swinburn, BA, Sacks, G, Hall, KD et al. (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378, 804814.
5. Berrington de Gonzalez, A (2010) Body-Mass index and mortality among 1·46 million white adults. N Engl J Med 365, 22112219.
6. Zimmet, P, Alberti, KG & Shaw, J (2001) Global and societal implications of the diabetes epidemic. Nature 414, 782787.
7. Hotamisligil, GS, Shargill, NS & Spiegelman, BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259, 8791.
8. Weisberg, SP, McCann, D, Desai, M et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 17961808.
9. Xu, H, Barnes, GT, Yang, Q et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112, 18211830.
10. Morand, EF, Leech, M & Bernhagen, J (2006) MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis. Nat Rev Drug Discov 5, 399410.
11. Serre-Beinier, V, Toso, C, Morel, P et al. (2011) Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice. J Endocrinol 206, 297306.
12. Koska, J, Stefan, N, Dubois, S et al. (2009) mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action. Int J Obes (Lond) 33, 842850.
13. Kahn, BB, Flier, JS (2000) Obesity and insulin resistance. J Clin Invest 106, 473481.
14. de Luca, C & Olefsky, JM (2008) Inflammation and insulin resistance. FEBS Lett 582, 97105.
15. Taniguchi, CM, Kondo, T, Sajan, M et al. (2006) Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta. Cell Metab 3, 343353.
16. Abel, ED, Peroni, O, Kim, JK et al. (2001) Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409, 729733.
17. Schenk, S, Saberi, M & Olefsky, JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118, 29923002.
18. Duncan, RE, Ahmadian, M, Jaworski, K et al. (2007) Regulation of lipolysis in adipocytes. Annu Rev Nutr 27, 79101.
19. Shulman, GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106, 171176.
20. Schwarz, JM, Linfoot, P, Dare, D et al. (2003) Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 77, 4350.
21. Brown, MS & Goldstein, JL (2008) Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 7, 9596.
22. Wellen, KE & Hotamisligil, GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115, 11111119.
23. Schmidt, MI, Duncan, BB, Sharrett, AR et al. (1999) Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 353, 16491652.
24. Pradhan, AD, Manson, JE, Rifai, N et al. (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286, 327334.
25. Fantuzzi, G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115, 911919.
26. Suganami, T & Ogawa, Y (2010) Adipose tissue macrophages: their role in adipose tissue remodeling. J Leukoc Biol 88, 3339.
27. Zhang, Y, Proenca, R, Maffei, M et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425432.
28. Maeda, K, Okubo, K, Shimomura, I et al. (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 221, 286289.
29. Thompson, BR, Lobo, S & Bernlohr, DA (2010) Fatty acid flux in adipocytes: the in's and out's of fat cell lipid trafficking. Mol Cell Endocrinol 318, 2433.
30. Suganami, TNJ & Ogawa, Y (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes; role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25, 20622068.
31. Hotamisligil, GS, Murray, DL, Choy, LN et al. (1994) Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci USA 91, 48544858.
32. Uysal, KT, Wiesbrock, SM, Marino, MW et al. (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389, 610614.
33. Hotamisligil, GS, Arner, P, Caro, JF et al. (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95, 24092415.
34. Bruun, JM, Helge, JW, Richelsen, B et al. (2006) Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am J Physiol Endocrinol Metab 290, E961E967.
35. Cancello, R, Henegar, C, Viguerie, N et al. (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54, 22772286.
36. Permana, PA, Menge, C & Reaven, PD (2006) Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun 341, 507514.
37. Antuna-Puente, B, Feve, B, Fellahi, S et al. (2008) Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 34, 211.
38. Lumeng, C, Deyoung, SM & Saltiel, AR (2006) Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am J Physiol Endocrinol Metab 292, 166174.
39. Solinas, G & Karin, M (2010) JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB J 24, 25962611.
40. Hirosumi, J, Tuncman, G, Chang, L et al. (2002) A central role for JNK in obesity and insulin resistance. Nature 420, 333336.
41. Tuncman, G, Hirosumi, J, Solinas, G et al. (2006) Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci USA 103, 1074110746.
42. Sabio, G, Das, M, Mora, A et al. (2007) A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science 322, 15391543.
43. Solinas, G, Vilcu, C, Neels, JG et al. (2007) JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 6, 386397.
44. Arkan MC, HA & Greten, FR (2005) IKK-beta links inflammation to obesity induced insulin resistance. Nat Med 11, 191198.
45. Medzhitov, R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1, 135145.
46. Shi, H, Kokoeva, MV, Inouye, K et al. (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116, 30153025.
47. Tsukumo, DM, Carvalho-Filho, MA, Carvalheira, JB et al. (2007) Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56, 19861998.
48. Saberi, M, Woods, NB, de Luca, C et al. (2009) Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab 10, 419429.
49. Harford, KA, Reynolds, CM, McGillicuddy, FC et al. (2011) Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 70, 408417.
50. Kono, H & Rock, KL (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8, 279289.
51. Weisberg, SP, Hunter, D, Huber, R et al. (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116, 115124.
52. Osborn, O & Olefsky, JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18, 363374.
53. Mosser, DM & Edwards, JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8, 958969.
54. Edwards, JP, Zhang, X, Frauwirth, KA et al. (2006) Biochemical and functional characterization of three activated macrophage populations. J Leukoc Biol 80, 12981307.
55. Lumeng, CN, Bodzin, JL & Saltiel, AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117, 175184.
56. Lumeng, CN, Deyoung, SM, Bodzin, JL et al. (2007) Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56, 1623.
57. Nguyen, MT, Favelyukis, S, Nguyen, AK et al. (2007) 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. J Biol Chem 282, 3527935292.
58. Patsouris, D, Li, PP, Thapar, D et al. (2008) Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 8, 301309.
59. Shaul, ME, Bennett, G, Strissel, KJ et al. (2010) Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet–induced obesity in mice. Diabetes 59, 11711181.
60. Westcott, DJ, Delproposto, JB, Geletka, LM et al. (2009) MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206, 31433156.
61. Zeyda, M, Gollinger, K, Kriehuber, E et al. (2010) Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression. Int J Obes (Lond) 34, 16841694.
62. Li, P, Lu, M, Nguyen, MT et al. (2010) Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J Biol Chem 285, 1533315345.
63. Schneemann, M & Schoeden, G (2007) Macrophage biology and immunology: man is not a mouse. J Leukoc Biol 81, 579 -discussion 80.
64. Zeyda, M & Stulnig, TM (2007) Adipose tissue macrophages. Immunol Lett 112, 6167.
65. Bourlier, V, Zakaroff-Girard, A, Miranville, A et al. (2008) Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 117, 806815.
66. Aron-Wisnewsky, J, Tordjman, J, Poitou, C et al. (2009) Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 94, 46194623.
67. Wentworth, JM, Naselli, G, Brown, WA et al. (2010) Pro-inflammatory CD11c + CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59, 16481656.
68. Bouhlel, MA, Derudas, B, Rigamonti, E et al. (2007) PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6, 137143.
69. Prieur, X, Roszer, T & Ricote, M (2010) Lipotoxicity in macrophages: evidence from diseases associated with the metabolic syndrome. Biochim Biophys Acta 1801, 327337.
70. Rosen, ED, Sarraf, P, Troy, AE et al. (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4, 611617.
71. Koutnikova, H, Cock, TA, Watanabe, M et al. (2003) Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice. Proc Natl Acad Sci USA 100, 1445714462.
72. Huang, JT, Welch, JS, Ricote, M et al. (1999) Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 400, 378382.
73. Odegaard, JI, Ricardo-Gonzalez, RR, Goforth, MH et al. (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447, 11161120.
74. Stienstra, R, Duval, C, Muller, M et al. (2007) PPARs, obesity, and inflammation. PPAR Res 2007, 95974.
75. Guri, AJ, Hontecillas, R, Ferrer, G et al. (2008) Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue. J Nutr Biochem 19, 216228.
76. Bassaganya-Riera, J, Misyak, S, Guri, AJ et al. (2009) PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation. Cell Immunol 258, 138146.
77. Prieur, X, Mok, CY, Velagapudi, VR et al. (2011) Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes 60, 797809.
78. Koliwad, SK, Streeper, RS, Monetti, M et al. (2010) DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation. J Clin Invest 120, 756767.
79. Cinti, S, Mitchell, G, Barbatelli, G et al. (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46, 23472355.
80. Alkhouri, N, Gornicka, A, Berk, MP et al. (2010) Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 285, 34283438.
81. Hosogai, N, Fukuhara, A, Oshima, K et al. (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56, 901911.
82. Kabon, B, Nagele, A, Reddy, D et al. (2004) Obesity decreases perioperative tissue oxygenation. Anesthesiology 100, 274280.
83. Ye, J, Gao, Z, Yin, J et al. (2007) Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 293, E1118E1128.
84. Sun, KKC & Scherer, PE (2011) Adipose tissue remodelling and obesity. J Clin Invest 121, 20942100.
85. Halberg, N, Khan, T, Trujillo, ME et al. (2009) Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29, 44674483.
86. O'Rourke, RW, White, AE, Metcalf, MD et al. (2011) Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia 54, 14801490.
87. Charo, IF & Ransohoff, RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354, 610621.
88. Gerard, C & Rollins, BJ (2001) Chemokines and disease. Nat Immunol 2, 108115.
89. Zlotnik, A, Yoshie, O & Nomiyama, H (2006) The chemokine and chemokine receptor superfamilies and their molecular evolution. Genome Biol 7, 243.
90. Chavey, C & Fajas, L (2009) CXCL5 drives obesity to diabetes, and further. Aging (Albany NY) 1, 674677.
91. Rull, A, Camps, J, Alonso-Villaverde, C et al. (2010) Insulin resistance, inflammation, and obesity: role of monocyte chemoattractant protein-1 (or CCL2) in the regulation of metabolism. Mediators Inflamm 10, 11551166.
92. Sartipy, P & Loskutoff, DJ (2003) Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 100, 72657270.
93. Chen, A, Mumick, S, Zhang, C et al. (2005) Diet induction of monocyte chemoattractant protein-1 and its impact on obesity. Obes Res 13, 13111320.
94. Kanda, H, Tateya, S, Tamori, Y et al. (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116, 14941505.
95. Kamei, N, Tobe, K, Suzuki, R et al. (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281, 2660226614.
96. Inouye, KE, Shi, H, Howard, JK et al. (2007) Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue. Diabetes 56, 22422250.
97. Digby, JE, McNeill, E, Dyar, OJ et al. (2010) Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin. Atherosclerosis 209, 8995.
98. Shah, R, Hinkle, CC, Ferguson, JF et al. (2011) Fractalkine is a novel human adipochemokine associated with type 2 diabetes. Diabetes 60, 15121518.
99. Boisvert, WA, Santiago, R, Curtiss, LK et al. (1998) A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 101, 353363.
100. Boisvert, WA, Rose, DM, Johnson, KA et al. (2006) Up-regulated expression of the CXCR2 ligand KC/GRO-alpha in atherosclerotic lesions plays a central role in macrophage accumulation and lesion progression. Am J Pathol 168, 13851395.
101. Straczkowski, M, Dzienis-Straczkowska, S, Stepien, A et al. (2002) Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. J Clin Endocrinol Metab 87, 46024606.
102. Neels, JG, Badeanlou, L, Hester, KD et al. (2009) Keratinocyte-derived chemokine in obesity: expression, regulation, and role in adipose macrophage infiltration and glucose homeostasis. J Biol Chem 284, 2069220698.
103. Kitade, H, Sawamoto, K, Nagashimada, M et al. (2012) CCR5 Plays a Critical Role in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Both Macrophage Recruitment and M1/M2 Status. Diabetes
104. Huber, J, Kiefer, FW, Zeyda, M et al. (2008) CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. J Clin Endocrinol Metab 93, 32153221.
105. Calandra, T, Bernhagen, J, Mitchell, RA et al. (1994) The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 179, 18951902.
106. Baugh, JA & Bucala, R (2002) Macrophage migration inhibitory factor. Crit Care Med 30, 2735.
107. Calandra, T & Roger, T (2003) Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 3, 791800.
108. Lue, H, Thiele, M, Franz, J et al. (2007) Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity. Oncogene 26, 50465059.
109. Roger, T, David, J, Glauser, MP et al. (2001) MIF regulates innate immune responses through modulation of Toll-like receptor 4. Nature 414, 920924.
110. Toh, ML, Aeberli, D, Lacey, D et al. (2006) Regulation of IL-1 and TNF receptor expression and function by endogenous macrophage migration inhibitory factor. J Immunol 177, 48184825.
111. Mitchell, RA, Liao, H, Chesney, J et al. (2002) Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response. Proc Natl Acad Sci USA 99, 345350.
112. Gregory, JL, Morand, EF, McKeown, SJ et al. (2006) Macrophage migration inhibitory factor induces macrophage recruitment via CC chemokine ligand 2. J Immunol 177, 80728079.
113. Toso, C, Emamaullee, JA, Merani, S et al. (2008) The role of macrophage migration inhibitory factor on glucose metabolism and diabetes. Diabetologia 51, 19371946.
114. Bernhagen, J, Krohn, R, Lue, H et al. (2007) MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 13, 587596.
115. Lue, H, Dewor, M, Leng, L et al. (2011) Activation of the JNK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on CXCR4 and CD74. Cell Signal 23, 135144.
116. Fan, H, Hall, P, Santos, LL et al. (2011) Macrophage migration inhibitory factor and CD74 regulate macrophage chemotactic responses via MAPK and Rho GTPase. J Immunol 186, 49154924.
117. Ghanim, H, Aljada, A, Hofmeyer, D et al. (2004) Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 110, 15641571.
118. Dandona, P, Aljada, A, Ghanim, H et al. (2004) Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. J Clin Endocrinol Metab 89, 50435047.
119. Church, TS, Willis, MS, Priest, EL et al. (2005) Obesity, macrophage migration inhibitory factor, and weight loss. Int J Obes (Lond) 29, 675681.
120. Vozarova, B, Stefan, N, Hanson, R et al. (2002) Plasma concentrations of macrophage migration inhibitory factor are elevated in Pima Indians compared to Caucasians and are associated with insulin resistance. Diabetologia 45, 17391741.
121. Skurk, T, Herder, C, Kraft, I et al. (2005) Production and release of macrophage migration inhibitory factor from human adipocytes. Endocrinology 146, 10061011.
122. Sakaue, S, Ishimaru, S, Hizawa, N et al. (2006) Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity. Int J Obes (Lond) 30, 238242.
123. Yabunaka, N, Nishihira, J, Mizue, Y et al. (2000) Elevated serum content of macrophage migration inhibitory factor in patients with type 2 diabetes. Diabetes Care 23, 256258.
124. Herder, C, Kolb, H, Koenig, W et al. (2006) Association of systemic concentrations of macrophage migration inhibitory factor with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg, Survey 4 (KORA S4). Diabetes Care 29, 368371.
125. Herder, C, Klopp, N, Baumert, J et al. (2008) Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case-Cohort Study, 1984–2002. Diabetologia 51, 276284.
126. Aslani, S, Hossein-nezhad, A, Maghbooli, Z et al. (2011) Genetic variation in macrophage migration inhibitory factor associated with gestational diabetes mellitus and metabolic syndrome. Horm Metab Res 43, 557561.
127. Waeber, G, Calandra, T, Roduit, R et al. (1997) Insulin secretion is regulated by the glucose-dependent production of islet beta cell macrophage migration inhibitory factor. Proc Natl Acad Sci USA 94, 47824787.
128. Saksida, T, Stosic-Grujicic, S, Timotijevic, G et al. (2011). Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. Immunol Cell Biol 169, 156163.
129. Hirokawa, J, Sakaue, S, Tagami, S et al. (1997) Identification of macrophage migration inhibitory factor in adipose tissue and its induction by tumor necrosis factor-alpha. Biochem Biophys Res Commun 235, 9498.
130. Hirokawa, J, Sakaue, S, Furuya, Y et al. (1998) Tumor necrosis factor-alpha regulates the gene expression of macrophage migration inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes. J Biochem 123, 733739.
131. Sakaue, S, Nishihira, J, Hirokawa, J et al. (1999) Regulation of macrophage migration inhibitory factor (MIF) expression by glucose and insulin in adipocytes in vitro. Mol Med 5, 361371.
132. Atsumi, T, Cho, YR, Leng, L et al. (2007) The proinflammatory cytokine macrophage migration inhibitory factor regulates glucose metabolism during systemic inflammation. J Immunol 179, 53995406.
133. Ikeda, D, Sakaue, S, Kamigaki, M et al. (2008) Knockdown of macrophage migration inhibitory factor disrupts adipogenesis in 3T3-L1 cells. Endocrinology 149, 60376042.
134. Verschuren, L, Kooistra, T, Bernhagen, J et al. (2009) MIF deficiency reduces chronic inflammation in white adipose tissue and impairs the development of insulin resistance, glucose intolerance, and associated atherosclerotic disease. Circ Res 105, 99107.

Keywords

Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

  • Orla M. Finucane (a1) (a2), Clare M. Reynolds (a2), Fiona C. McGillicuddy (a2) and Helen M. Roche (a2)

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