Molecular mechanisms underlying the ameliorative effects of crocodile head-derived bioactive peptides on DEX-induced muscle atrophy: insights from proteomics and gut microbiota analysis

Muscle atrophy is relatively common among older adults and can markedly impair their physical function and overall quality of life. Crocodile head-derived bioactive peptides (CP), with high bioavailability and low allergenicity, show promise as a nutritional intervention. This study aimed to investigate the alleviating effects of CP on muscle atrophy and clarify their underlying action mechanisms. Results demonstrated that CP alleviated muscle atrophy-related weight loss, increasing gastrocnemius, quadriceps, and tibialis anterior muscle indices by 60%, 33%, and 28%. The lean body mass percentage increased by 3.7%, while the body fat rate decreased by 6%. Following CP administration, grip strength, motion displacement, and exhaustion time in mouse recovered to 1.71 N, 495 m, and 1130 s. Proteomic analysis revealed that CP potentially ameliorates muscle atrophy by modulating the AMPK signaling pathway to restore energy metabolism homeostasis, activating autophagy to clear dysfunctional organelles, and reprogramming lipid metabolism to suppress ectopic fat deposition in muscle tissue. Analysis of the gut microbiota further indicated that CP intervention significantly increased the abundance of beneficial bacteria, including Muribaculaceae, Allobaculum, Lactobacillus, Monoglobus, and Dubosiella. In conclusion, CP likely mitigates muscle atrophy progression via multi-target mechanisms, including modulation of energy metabolism, autophagy, lipid metabolism, and the gut microenvironment.