Monocyte Chemoattractant Protein‐1 in Obesity and Type 2 Diabetes. Insulin Sensitivity Study

OBJECTIVE: Our goal was to test any association between human plasma circulating levels of monocyte chemoattractant protein-1 (cMCP-1) and insulin resistance and to compare monocyte chemoattractant protein-1 (MCP-1) adipose tissue gene expression and cMCP-1 in relation with inflammatory markers. RESEARCH METHODS AND PROCEDURES: cMCP-1 was measured in n = 116 consecutive control male subjects to whom an insulin sensitivity (S(i)) test was performed. Circulating levels of soluble CD14, soluble tumor necrosis factor receptor type 2 (sTNFR2), soluble interleukin-6 (sIL-6), and adiponectin also were measured. Subcutaneous adipose tissue samples were obtained from n = 107 non-diabetic and type 2 diabetic subjects with different degrees of obesity. Real-time polymerase chain reaction was used to measure gene expression of MCP-1, CD68, tumor necrosis factor-alpha (TNF-alpha), and its receptor TNFR2. RESULTS: In the S(i) study, no independent effect of cMCP-1 levels on insulin sensitivity was observed. In the expression study, in non-diabetic subjects, MCP-1 mRNA had a positive correlation with BMI (r = 0.407, p = 0.003), TNF-alpha mRNA (r = 0.419, p = 0.002), and TNFR2 mRNA (r = 0.410, p = 0.003). In these subjects, cMCP-1 was found to correlate with waist-to-hip ratio (r = 0.322, p = 0.048). In patients with type 2 diabetes, MCP-1 mRNA was up-regulated compared with non-diabetic subjects. TNF-alpha mRNA was found to independently contribute to MCP-1 mRNA expression. In this group, CD68 mRNA was found to correlate with BMI (r = 0.455, p = 0.001). DISCUSSION: cMCP-1 is not associated with insulin sensitivity in apparently healthy men. TNF-alpha is the inflammatory cytokine associated with MCP-1 expression in subcutaneous adipose tissue.