Pioglitazone Improves Aerobic Capacity and Skeletal Muscle Energy Metabolism in Patients with Metabolic Syndrome

Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). The aim of the study was to investigate the effects of pioglitazone on aerobic capacity and skeletal muscle energy metabolism in patients with MetS. Fourteen patients with MetS participated in the study and received 15 mg/day pioglitazone for 4 months. To assess skeletal muscle energy metabolism, intramyocellular lipid (IMCL) in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus-magnetic resonance spectroscopy, respectively. Pioglitazone significantly increased peak VO2 and anaerobic threshold in patients with MetS. IMCL content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in AT, submaximal exercise capacity, closely correlated with the decrease in IMCL content after pioglitazone treatment. In conclusion, pioglitazone significantly improved aerobic capacity and skeletal muscle energy metabolism in patients with MetS. The beneficial effect of pioglitazone on aerobic capacity might be, at least in part, via improved fatty acid metabolism in skeletal muscle. Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). The aim of the study was to investigate the effects of pioglitazone on aerobic capacity and skeletal muscle energy metabolism in patients with MetS. Fourteen patients with MetS participated in the study and received 15 mg/day pioglitazone for 4 months. To assess skeletal muscle energy metabolism, intramyocellular lipid (IMCL) in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus-magnetic resonance spectroscopy, respectively. Pioglitazone significantly increased peak VO2 and anaerobic threshold in patients with MetS. IMCL content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in AT, submaximal exercise capacity, closely correlated with the decrease in IMCL content after pioglitazone treatment. In conclusion, pioglitazone significantly improved aerobic capacity and skeletal muscle energy metabolism in patients with MetS. The beneficial effect of pioglitazone on aerobic capacity might be, at least in part, via improved fatty acid metabolism in skeletal muscle.