Horm Metab Res 2011; 43(09): 642-645
DOI: 10.1055/s-0031-1283150
Humans, Clinical
Georg Thieme Verlag KG Stuttgart · NewYork

Elevated Levels of Macrophage Migration Inhibitory Factor in Women with Metabolic Syndrome

H.- R. Kim
1   Department of Anatomy and SNUMRC, Seoul National University College of Medicine, Seoul, Republic of Korea
,
S.- A. Lee
2   Department of Microbiology and Immunology, Cancer Research Institute, Liver Research Institute and SNUMRC, Seoul National University College of Medicine, Seoul, Republic of Korea
,
H.J. Kim
3   Department of Family Medicine, College of Medicine, Jeju National University, Jeju, Republic of Korea
,
M. H. Kong
3   Department of Family Medicine, College of Medicine, Jeju National University, Jeju, Republic of Korea
,
Y. R. Kim
4   Department of Laboratory Medicine, College of Medicine, Jeju National University, Jeju, Republic of Korea
,
S. H. Kang
4   Department of Laboratory Medicine, College of Medicine, Jeju National University, Jeju, Republic of Korea
,
K.- H. Lee
5   Department of Microbiology, College of Medicine, Jeju National University, Jeju, Republic of Korea
,
L. Leng
6   Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
,
B.- J. Lee
7   Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
,
C. G. Park
2   Department of Microbiology and Immunology, Cancer Research Institute, Liver Research Institute and SNUMRC, Seoul National University College of Medicine, Seoul, Republic of Korea
,
Y.- H. Kook
2   Department of Microbiology and Immunology, Cancer Research Institute, Liver Research Institute and SNUMRC, Seoul National University College of Medicine, Seoul, Republic of Korea
,
B.- J. Kim
2   Department of Microbiology and Immunology, Cancer Research Institute, Liver Research Institute and SNUMRC, Seoul National University College of Medicine, Seoul, Republic of Korea
,
R. Bucala
6   Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
› Author Affiliations
Further Information

Publication History

received 15 May 2011

accepted 21 June 2011

Publication Date:
05 August 2011 (online)

Abstract

Metabolic syndrome is a complex clinical disorder characterized by obesity, a disturbance of glucose metabolism, dyslipidemia, and hypertension, leading to increased cardiovascular risk. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced both by innate immune cells and by adipocytes, and it plays an important role in inflammatory and cardiovascular diseases. The goal of this study was to evaluate the expression of circulating MIF in patients with metabolic syndrome. A study was conducted involving 172 persons who attended the Jeju National University Hospital Health Promotion Center. Among the 172 subjects, 88 patients with metabolic syndrome and 84 healthy control subjects were included. Serum MIF levels were considerably higher in patients with metabolic syndrome than in healthy subjects (mean±SEM, 1413.0-pg/ml±102.6 vs. 1077.0-pg/ml±-91.3, p=0.016). Among the metabolic syndrome patients, MIF levels were significantly increased in women (1403.0-pg/ml±114.2 vs. 921.3pg/ml±117.3, p=0.005), but not in men. Even after further linear regression adjustment for age and body mass index, the expression of MIF for women with metabolic syndrome was still clearly elevated when compared to healthy subjects (p=0.011). Circulating MIF concentrations showed a gender disparity between healthy and metabolic syndrome subjects. An elevation of systemic MIF in women with metabolic syndrome may contribute to pathogenesis of metabolic syndrome or to the development of metabolic syndrome-related diseases, such as atherosclerosis and type 2 diabetes mellitus.

 
  • References

  • 1 Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr 1956; 4: 20-34
  • 2 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
  • 3 Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 2003; 3: 791-800
  • 4 Morand EF, Leech M, Bernhagen J. MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis. Nat Rev Drug Discov 2006; 5: 399-410
  • 5 Zernecke A, Bernhagen J, Weber C. Macrophage migration inhibitory factor in cardiovascular disease. Circulation 2008; 117: 1594-1602
  • 6 Atsumi T, Cho YR, Leng L, McDonald C, Yu T, Danton C, Hong EG, Mitchell RA, Metz C, Niwa H, Takeuchi J, Onodera S, Umino T, Yoshioka N, Koike T, Kim JK, Bucala R. The proinflammatory cytokine macrophage migration inhibitory factor regulates glucose metabolism during systemic inflammation. J Immunol 2007; 179: 5399-5406
  • 7 Verschuren L, Kooistra T, Bernhagen J, Voshol PJ, Ouwens DM, van Erk M, de Vries-van der Weij J, Leng L, van Bockel JH, van Dijk KW, Fingerle-Rowson G, Bucala R, Kleemann R. MIF deficiency reduces chronic inflammation in white adipose tissue and impairs the development of insulin resistance, glucose intolerance, and associated atherosclerotic disease. Circ Res 2009; 105: 99-107
  • 8 Kleemann R, Bucala R. Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities. Mediators Inflamm. 2010 610479
  • 9 Noels H, Bernhagen J, Weber C. Macrophage migration inhibitory factor: a noncanonical chemokine important in atherosclerosis. Trends Cardiovasc Med 2009; 19: 76-86
  • 10 Herder C, Kolb H, Koenig W, Haastert B, Muller-Scholze S, Rathmann W, Holle R, Thorand B, Wichmann HE. 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 2006; 29: 368-371
  • 11 Aslani S, Hossein-Nezhad A, Maghbooli Z, Mirzaei K, Karimi F. Genetic Variation in Macrophage Migration Inhibitory Factor Associated with Gestational Diabetes Mellitus and Metabolic Syndrome. Horm Metab Res April 21 [Epub ahead of print]
  • 12 Herder C, Klopp N, Baumert J, Muller M, Khuseyinova N, Meisinger C, Martin S, Illig T, Koenig W, Thorand B. 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 2008; 51: 276-284
  • 13 Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356-359
  • 14 Regitz-Zagrosek V, Lehmkuhl E, Mahmoodzadeh S. Gender aspects of the role of the metabolic syndrome as a risk factor for cardiovascular disease. Gend Med 2007; 4 (Suppl B) S162-S177
  • 15 Burger-Kentischer A, Goebel H, Seiler R, Fraedrich G, Schaefer HE, Dimmeler S, Kleemann R, Bernhagen J, Ihling C. Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis. Circulation 2002; 105: 1561-1566
  • 16 Vozarova B, Stefan N, Hanson R, Lindsay RS, Bogardus C, Tataranni PA, Metz C, Bucala R. Plasma concentrations of macrophage migration inhibitory factor are elevated in Pima Indians compared to Caucasians and are associated with insulin resistance. Diabetologia 2002; 45: 1739-1741
  • 17 Makino A, Nakamura T, Hirano M, Kitta Y, Sano K, Kobayashi T, Fujioka D, Saito Y, Watanabe K, Watanabe Y, Kawabata K, Obata JE, Kugiyama K. High plasma levels of macrophage migration inhibitory factor are associated with adverse long-term outcome in patients with stable coronary artery disease and impaired glucose tolerance or type 2 diabetes mellitus. Atherosclerosis 2010; 213: 573-578
  • 18 Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol 2006; 95: 136-147
  • 19 Ashcroft GS, Mills SJ, Lei K, Gibbons L, Jeong MJ, Taniguchi M, Burow M, Horan MA, Wahl SM, Nakayama T. Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor. J Clin Invest 2003; 111: 1309-1318
  • 20 Burger HG, Dudley EC, Robertson DM, Dennerstein L. Hormonal changes in the menopause transition. Recent Prog Horm Res 2002; 57: 257-275
  • 21 Misso ML, Jang C, Adams J, Tran J, Murata Y, Bell R, Boon WC, Simpson ER, Davis SR. Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy. Menopause 2005; 12: 210-215