Abstract 2201: Impaired Skeletal Muscle Energy Metabolism Limits Aerobic Exercise Capacity in Patients with Metabolic Syndrome
Insulin resistance is associated with the limited exercise capacity, which can be an independent predictor for cardiovascular morbidity and mortality. However, the underlying mechanism of limiting exercise capacity in this setting remains unknown. We assessed the hypothesis that the limited exercise capacity is due to the defects in mitochondrial energy metabolism in skeletal muscle of patients with metabolic syndrome (MetS). The incremental exercise tests with a cycle ergometer were performed in 12 patients with MetS diagnosed by the NCEPIII criteria, and 10 age- and sex-matched control subjects with no habitual exercise. 31P-magnetic resonance spectroscopy (MRS) was performed to measure muscular phosphocreatine (PCr) and inorganic phosphorus during unilateral plantar flexion (0.67Hz for 4 min) with a constant load of 20% one-repetition-maximum. 1H-MRS was performed in resting leg muscle to measure intramyocellular lipid (IMCL) content to assess the balance between uptake and oxidation of fatty acid. Lean-adjusted peak oxygen uptake (peakVO2; 34.5±6.6 vs 41.4±8.4 mL/kg/min, P<0.05) and anaerobic threshold (AT; 18.0±2.4 vs 23.1±4.0 mL/kg/min, P<0.01) were significantly lower in MetS compared to control subjects. Maximal PCr breakdown during plantar flexion was significantly higher in MetS (34±13 vs 22±11%, P<0.05), indicating that ATP production in skeletal muscle mitochondria is decreased during exercise because muscular PCr levels are maintained by ATP produced by mitochondrial oxidative phosphorylation. IMCL content was significantly increased in MetS (4.4±1.7 vs 2.0±1.7 mmol/kg wet weight, P<0.01). There was a negative relationship between AT and maximal PCr breakdown (r=−0.56, P<0.01) or IMCL content (r=−0.49, P<0.05), indicating that the basis for lowered aerobic exercise capacity in MetS might be the impairment of skeletal muscle metabolic properties. There was also a significant correlation between maximal PCr breakdown and IMCL content (r=0.54, P<0.01). Patients with MetS had lowered aerobic exercise capacity, which might be due to impaired skeletal muscle mitochondrial oxidative phosphorylation and dysregulation of intramyocellular fatty acid metabolism.