l-Citrulline Supplementation-Increased Skeletal Muscle PGC-1α Expression Is Associated with Exercise Performance and Increased Skeletal Muscle Weight

Supplementation with l-citrulline upregulates skeletal muscle PGC-1α levels resulting in higher skeletal muscle weight that improves time to exhaustion during exercise.

Six-week-old ICR mice were orally supplemented with l-citrulline (250 mg kg-1 ) daily, and their performance in weight-loaded swimming exercise every other day for 15 days, was evaluated. In addition, mice muscles were weighed and evaluated for the expression of PGC-1α and PGC-1α-regulated genes. Mice orally supplemented with l-citrulline had significantly higher gastrocnemius and biceps femoris muscle mass. Although not statistically significant, l-citrulline prolonged the swimming time to exhaustion. PGC-1α upregulation was associated with vascular endothelial growth factor α (VEGFα) and insulin-like growth factor 1 (IGF-1) upregulation. VEGFα and IGF-1 are important for angiogenesis and muscle growth, respectively, and are regulated by PGC-1α. Treatment with NG-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nitric oxide synthesis inhibitor, suppressed the l-citrulline-induced PGC-1α upregulation in vitro.