Effect of Short-Term Free Fatty Acids Elevation on Mitochondrial Function in Skeletal Muscle of Healthy Individuals

Context: Mitochondrial dysfunction has been proposed as an underlying mechanism in the pathogenesis of insulin resistance and type 2 diabetes mellitus. Objective: To determine whether mitochondrial dysfunction plays a role in the free fatty acid (FFA)-induced impairment in insulin action in skeletal muscle of healthy subjects. Design: Eleven lean normal glucose tolerant individuals received 8 h lipid and saline infusion on separate days with a euglycemic insulin clamp during the last 2 h. Vastus lateralis muscle biopsies were performed at baseline and after 6 h lipid or saline infusion. Inner mitochondrial membrane potential (Ψm) and mitochondrial mass were determined ex vivo by confocal microscopy. Results: Compared with saline infusion, lipid infusion reduced whole-body glucose uptake by 22% (P < 0.05). Ψm decreased by 33% (P < 0.005) after lipid infusion and the decrement in Ψm correlated with change in plasma FFA after lipid infusion (r = 0.753; P < 0.005). Mitochondrial content and morphology did not...