Enhanced Skeletal Muscle Lipid Oxidative Efficiency in Insulin-Resistant vs Insulin-Sensitive Nondiabetic, Nonobese Humans

Context: Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals. Objective: The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals. Design and Volunteers: In 13 insulin-sensitive [by Matsuda index (MI) (22.6 +/- 0.6 [SE] kg/m(2)); 23 +/- 1 years; MI 5.9 +/- 0.1] and 13 insulin-resistant (23.2 +/- 0.6kg/m(2); 23 +/- 3 years; MI 2.2 +/- 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed. Main Outcome Measures: Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and beta-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((CO2)-C-14 and C-14-acid soluble metabolites production) at 4 [1-C-14] palmitate concentrations (45-520 mu M) were also measured. Results: None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 +/- 0.4 vs 2.2 +/- 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to C-14-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 +/- 0.04 vs 0.12 +/- 0.02; P = .02). Conclusions: We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin resistance could be a potential mechanism to prevent further lipotoxicity. (J Clin Endocrinol Metab 98: E646-E653, 2013)