Wheat peptides improved sarcopenia by enhancing muscle protein synthesis in mice and zebrafish

The goal of this study was designed to investigate the alleviating effects and mechanisms of wheat peptides (WP) on dexamethasone (DEX)-induced sarcopenia in mice. Furthermore, this study sought to validate the anti -sarcopenic efficacy of peptides identified through integrated in silico screening and peptidomic analysis in DEX-induced zebrafish model. The findings exhibited statistically significant enhancements in skeletal muscle strength (grip strength and swimming exhaustive time) and mass (gastrocnemius and soleus indexes) with oral administration of WP. In addition, metabolomics analysis identified N1-Methyl-2-Pyridone-5-Carboxamide and creatine are the crucial metabolites regulated by WP, associated with enhancements in muscle functionality in mice experiencing sarcopenia. WP counteract DEX-induced suppression of fibroblast growth factor receptor 1 (FGFR1) expression, subsequently regulated downstream mammalian target of rapamycin complex 1 (mTORC1) expression, thereby stimulating muscle protein synthesis and ameliorating sarcopenia in mice. Furthermore, docking analysis indicated that WP-derived peptides characterized by high abundance and favorable PeptideRanker scores demonstrated strong binding with FGFR1. More importantly, Ser-Ser-Gly-Lys-Phe-Leu-Arg (SSGKFLR) exhibited the most robust binding affinities, which formed interactions with FGFR1 residues via hydrogen bonds, van der Waals forces, and electrostatic interactions. The anti -sarcopenic efficacy of SSGKFLR was further validated in DEX-induced zebrafish model. Those findings indicate that WP may serve as an effective dietary intervention approach to combat sarcopenia.