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

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. 921.3 pg/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.

Lipoprotein(A) Level and Mif Gene Variant Predict Incident Metabolic Syndrome and Mortality

“…Authors expressed the viewpoint that MetS is rather a consequence of interactions among different pathways. Collectively, our observations strongly suggest that the MIF gene variant contributes to the development of MetS or type 2 diabetes,27 28 and also that the MIF protein may sustain damage to its epitope/DNA under conditions of prolonged oxidative stress, rendering a portion of it to escape from immunoassay and to a failure of its genetic expression, which is protective against a pro-inflammatory state in two-thirds of carriers 32. The present and previous studies demonstrate that such oxidative damage to the MIF protein may be much more pronounced in one sex (confirmed in as yet unpublished observations) and that the involved gender may differ depending on ethnicity.…”

Sex-Specific Predictors of Metabolic Syndrome Independent of Its Components

“…Elevated MIF levels in relation to the likelihood of MetS was confined to women and, interestingly, not observed in men in the Korean study. 33 Available evidence in the literature, including the report by Cardaropoli et al, 34 supports the assumption that serum MIF protein may sustain inflammation-related damage, accompanied by few other proteins simultaneously involved in an autoimmune process.…”

Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies

“…Of note, plasma MIF concentrations tend to be higher in males than in females (26, 34), suggesting an inducing effect of male sex hormones. Indeed, circulating MIF levels are two to threefold higher in women with polycystic ovary syndrome (PCOS), an endocrine disorder characterized by elevated levels of androgens (31, 35).…”

“…A study by Kim et al (34) compared healthy Korean subjects (BMI 20.2 kg/m 2 ) without metabolic syndrome with patients with metabolic syndrome (BMI 27.2 kg/m 2 ) and found higher levels in patients than controls (1.4 ± 0.1 and 1.0 ± 0.1 ng/ml, respectively), which was significant in women but not in men. N.B.…”