BackgroundEndurance is an important capacity to sustain healthy lifestyles. Aged garlic extract (AGE) has been reported to exert endurance-enhancing effect in the clinical and animal studies, though little is known of its active ingredients and mechanism of action. ObjectiveThe current study investigated the potential effect of S-1-propenylcysteine (S1PC), a characteristic sulfur amino acid in AGE, on the swimming endurance of mice and examined its mechanism of action by a metabolomics-based approach. MethodsMale ICR mice (6 weeks old) were orally administered water (control) or S1PC (6.5 mg/kg/day) for 2 weeks and swimming duration to exhaustion was measured at 24 hours after the last administration. Non-targeted metabolomic analysis was conducted on the plasma samples obtained from mice following 40-minute submaximal swimming bouts. Subsequently, the enzyme activity of carnitine acyltransferase-1 (CPT-1) and the content of malonyl-coenzyme A (CoA), acetyl-CoA and adenosine triphosphate (ATP) were quantified in heart, skeletal muscles and liver of mice. ResultsThe duration time of swimming was substantially increased in the S1PC-treated mice as compared to the control group. Metabolomic analysis revealed significant alterations in the plasma level of the metabolites involved in the fatty acid metabolism, in particular medium- or long-chain acylcarnitines in the mice treated with S1PC. Moreover, administration of S1PC significantly enhanced the CPT-1 activity with the concomitant decrease in the malonyl-CoA content in the heart and skeletal muscles. These effects of S1PC were accompanied by the elevation of the acetyl-CoA and ATP levels to enhance the energy production in those tissues. ConclusionS1PC is a key constituent responsible for the endurance-enhancing effect of AGE. The present study suggests that S1PC helps provide the energy during the endurance exercise by increasing fatty acid metabolism via CPT-1 activation in the heart and skeletal muscles.