Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians

Abstract

Objective: In severely obese individuals and patients with diabetes accumulation and activation of macrophages in adipose tissue (AT) has been implicated in the development of obesity-associated complications including insulin resistance. We sought to determine whether in a healthy population adiposity, gender, age, or insulin action, are associated with adipose tissue macrophages (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 of estimated metabolic body size/min, by glucose clamp) were measured. We also measured expression in AT 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 CSF1R) was correlated with % 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 % body fat, age and sex. However, AT 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 AT macrophage activation.