
Activated macrophages secrete pro-inflammatory factors as TNF alpha and IL-6 which contribute to insulin resistance. Increased adipose tissue infiltration with macrophages has been described in the obese state. J Clin Invest. 2003 Dec;112(12):1785-8. MCP -1 is a chemokine that recruits monocytes to sites of inflammation. MCP-1 is expressed and secreted by adipocytes and stromal vascular cells in white adipose tissue. Obese rodents have higher circulating MCP-1 levels with increased adipose tissue expression of MCP-1. J Biol Chem. 2003 Nov 21;278(47):46654-6o
CP-1 can directly contribute to insulin resistance by decreasing insulin stimulated glucose uptake and insulin induced insulin receptor tyrosine phosphorylation. MCP-1 also decreases the expression of adipogenic genes thus inhibiting adipocyte growth and differentiation. Administration of MCP-1 to mice peripherally increases circulating monocytes, and increases monocyte accumulation in arteries with neo-intimal formation suggesting a role for MCP-1 in atherogenesis. Cardiovasc Res. 2003 Jan;57(1):178-85. Thiazolidinediones (rosiglitazone) treatment in a 6 week study in diabetic and non-diabetic obese patients demonstrated a reduction in MCP-1 and CRP revealing the potential anti-inflammatory properties of this group of drugs. J Clin Endocrinol Metab. 2004 Jun;89(6):2728-35