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

Mol Nutr Food Res. 2018 Jul;62(14):e1701043. doi: 10.1002/mnfr.201701043. Epub 2018 Jun 25.


Scope: l-citrulline has recently been reported as a more effective supplement for promoting intracellular nitric oxide (NO) production compared to l-arginine. Here, the effect of l-citrulline on skeletal muscle and its influence on exercise performance were investigated. The underlying mechanism of its effect, specifically on the expression of skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), was also elucidated.

Methods and results: 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.

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

Keywords: PGC-1α; exercise performance; l-citrulline; skeletal muscle weight; supplementation.