Leptin stimulation of COXIV is impaired in obese skeletal muscle myotubes

SUMMARY: OBJECTIVE: To investigate the effects of leptin on the mRNA abundance of key genes involved in fatty acid oxidation and mitochondrial biogenesis in cultured skeletal muscle myotubes derived from lean and obese individuals. RESEARCH METHODS AND PROCEDURES: Rectus abdominus muscle biopsies were obtained from surgical patients to establish primary skeletal muscle cell cultures. Two distinct primary cell culture groups were established (Lean and Obese) n = 7 in each group. Differentiated cultures were then exposed to leptin (2.5 μg/ml) for 6 h. mRNA expression was subsequently measured by real-time PCR analysis. RESULTS: Basal mRNA expression of βHAD, COXIII, COXIV, PGC-1α and SOCS3 in the cultured human skeletal muscle myotubes were similar, however, PDK4 mRNA was elevated (P < 0.05) in the myotubes derived from obese individuals. The addition of leptin resulted in a 2.5-fold increase in COXIV mRNA expression in the myotubes derived from Lean individuals only (P < 0.05). There was also a tendency for leptin to increase COXIII, βHAD and PDK4 mRNA expression in this same group. Leptin had no impact on the gene expression of all measured transcripts in myotubes derived from obese individuals. CONCLUSION: Short-term exposure of human skeletal muscle myotubes to leptin stimulated the expression of the mitochondrial enzyme COXIV in myotubes derived from lean individuals, an effect that was abrogated in myotubes derived from obese individuals. These data demonstrate a novel capacity for leptin to increase mitochondrial biogenesis and thus, a possible increased capacity for lipid oxidation and the persistence of a defect in leptin signalling in human myotubes cultured from obese individuals.