Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice

Obesity is currently considered as an epidemic in the western world, and it represents a major risk factor for life-threatening diseases such as heart attack, stroke, diabetes, and cancer. Taking advantage of DNA microarray technology, we tried to identify the molecules explaining the relationship between obesity and vascular disorders, comparing mRNA expression of about 12,000 genes in white adipose tissue between normal, high fat diet-induced obesity (DIO) and D-Trp(34) neuropeptide Y-induced obesity in mice. Expression of monocyte chemoattractant protein-1 (MCP-1) mRNA displayed a 7.2-fold increase in obese mice as compared with normal mice, leading to substantially elevated MCP-1 protein levels in adipocytes. MCP-1 levels in plasma were also increased in DIO mice, and a strong correlation between plasma MCP-1 levels and body weight was identified. We also showed that elevated MCP-1 protein levels in plasma increased the CD11b-positive monocyte/macrophage population in DIO mice. Furthermore, infusion of MCP-1 into lean mice increased the CD11b-positive monocyte population without inducing changes in body weight. Given the importance of MCP-1 in activation of monocytes and subsequent atherosclerotic development, these results suggest a novel role of adiposity in the development of vascular disorders.