Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects

Objective: Chronic inflammation observed in obesity has been reported to be implicated in the development of atherosclerosis. We screened candidate chemokines that link chronic inflammation and obesity. Research Methods and Procedures: Japanese overweight (n = 39, BMI 28.7 +/- 0.65 kg/m(2)) and normal-weight (n = 24, BMI 22.3 +/- 0.45 kg/m(2)) subjects were enrolled. Using antibody-based protein microarray, spot intensities of monocyte chemoattractant protein (MCP)-4, eotaxin, and eotaxin-2 correlated with anthropometric parameters. We further measured serum concentration of these chemokines and mRNA levels in adipose tissues obtained from volunteers. Results: Serum MCP-4 levels showed positive correlation with BMI (r = 0.318, p = 0.014), waist (r = 0.316, p = 0.018), and waist-to-hip ratio (WHR) (r = 0.264, p = 0.049). Furthermore, MCP-4 correlated with homeostasis model assessment of insulin resistance (r = 0.392, p = 0.002), high-sensitivity C-reactive protein (hsCRP) (r = 0.350, p = 0.006). In step-wise multiple regression analyses, hsCRP independently correlated with MCP-4 levels. The expression of MCP-4 mRNA in visceral adipose tissue positively correlates with BMI. Serum eotaxin levels correlate with BMI (r = 0.262, p = 0.045) and WHR (r = 0.383, p = 0.003). Serum eotaxin-2 levels correlated with BMI (r = 0.464, p < 0.001), waist (r = 0.333, p = 0.017), and WHR (r = 0.278, p = 0.048). However, eotaxin and eotaxin-2 levels did not show significant correlation with hsCRP. Discussion: Serum levels of MCP-4, eotaxin, and eotaxin-2, which belong to CC chemokine family and share CC chemokine receptor 3, correlated with BMI. These chemokines, especially MCP-4, may be critical molecules that link obesity and chronic inflammation.