ArticleCells2026
Combined Histidine and Proline Supplementation (HISPRO) Enhances Oxidative and Mitochondrial Function in Skeletal Muscle Through SIRT1-Associated Signaling.
Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Amino acids are key regulators of metabolism, their coordinated effects on skeletal muscle signaling and metabolic remodeling under physiological conditions remain incompletely understood. Here, we investigated whether 14 weeks of combined histidine and proline supplementation (HISPRO; 700 mg/kg) enhances skeletal muscle function through metabolic reprogramming in normal ICR mice. HISPRO significantly improved muscle performance compared with the control group, including grip strength, rota-rod, and treadmill. Histological and biochemical analyses revealed a shift toward oxidative muscle phenotype compared with the control group, with larger muscle fibers and succinate dehydrogenase-positive fibers. Consistently, HISPRO promoted mitochondrial biogenesis and oxidative metabolism compared with the control group, as evidenced by upregulation of mitochondrial regulatory genes, mitochondrial DNA copy number, citrate synthase activity, and oxidative phosphorylation (OXPHOS) complex levels in skeletal muscles. Mechanistically, HISPRO was associated with activation of the SIRT1-PGC1α-AMPK signaling axis compared with the control group, as evidenced by increased
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