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OBJECTIVE-In severely obese individuals and patients with diabetes, accumulation and activation of macrophages in adipose tissue has been implicated in the development of obesityassociated complications, including insulin resistance. We sought to determine whether in a healthy population, adiposity, sex, age, or insulin action is associated with adipose tissue macrophage content (ATMc) and/or markers of macrophage activation.
RESEARCH DESIGN AND METHODS-Subcutaneous ATMc from young adult Pima Indians with a wide range of adiposity (13-46% body fat, by whole-body dual-energy X-ray absorptiometry) and insulin action (glucose disposal rate 1.6-9 mg/kg estimated metabolic body size/min, by glucose clamp) were measured. We also measured expression in adipose tissue of factors implicated in macrophage recruitment and activation to determine any association with ATMc and insulin action.
RESULTS-ATMc, as assessed by immunohistochemistry (Mphi) and by macrophage-specific gene expression (CD68, CD11b, and CSFlR), were correlated with percent body fat, age, and female sex. Gene expression of CD68, CD11b, and CSF1R but not Mphi was correlated negatively with glucose disposal rate but not after adjustment for percent body fat, age, and sex. However, adipose tissue expression of plasminogen activator inhibitor type-1 (PAI-1) and CD11 antigen-like family member C (CD11c), markers produced by macrophages, were negatively correlated with adjusted glucose disposal rate (r = -0.28, P = 0.05 and r = -0.31, P = 0.03).
CONCLUSIONS-ATMc is correlated with age and adiposity but not with insulin action independent of adiposity in healthy human subjects. However, PAI-1 and CD11c expression are independent predictors of insulin action, indicating a possible role for adipose tissue macrophage activation. Diabetes 58: 385-393, 2009
Obesity is an inflammatory condition leading to chronic activation of an innate immune response (1). This inflammatory response has been implicated in the pathogenesis of obesityassociated complications, including atherosclerosis (2), nonalcoholic fatty liver disease (3), and insulin resistance (4). Adipose tissue is a primary site of obesity-induced inflammation and a complex organ containing adipocytes as well as connective tissue matrix, nerve tissue, stromal vascular cells, and immune cells. A cardinal feature of obesity-induced inflammation in adipose tissue is the recruitment of immune cells, specifically macrophages (5,6). Although the adipocyte is the defining cell of adipose tissue and does contribute to the production of inflammatory molecules (J), it appears that macrophages contribute substantially to the inflammatory...