Untargeted metabolomic reveals the changes in muscle metabolites of mice during exercise recovery and the mechanisms of whey protein and whey protein hydrolysate in promoting muscle repair.

Our previous study indicated that whey protein hydrolysate (WPH) showed effective anti-fatigue properties, but its regulatory mechanism on recovery from exercise in mice is unclear. In the present study, we divided the mice into control, WP, and WPH groups and allowed them to rest for 1 h and 24 h after exercise, respectively. The changes in muscle metabolites of mice in the recovery period were investigated using metabolomics techniques. The results showed that the WPH group significantly up-regulated 94 muscle metabolites within 1 h of rest, which was 1.96 and 2.61 times more than the control and WP groups, respectively. In detail, significant decreases in TCA cycle intermediates, lipid metabolites, and carbohydrate metabolites were observed in the control group during exercise recovery. In contrast, administration with WP and WPH enriched more amino acid metabolites within 1 h of rest, which might provide a more comprehensive metabolic environment for muscle repair. Moreover, the WPH group remarkably stimulated the enhancement of lipid, carbohydrate, and vitamin metabolites in the recovery period which might provide raw materials and energy for anabolic reactions. The result of the western blot further demonstrated that WPH could promote muscle repair via activating the Sestrin2/Akt/mTOR/S6K signaling pathway within 1 h of rest. These findings deepen our understanding of the regulatory mechanisms by WPH to promote muscle recovery and may serve as a reference for comprehensive assessments of protein supplements on exercise.