Metabolomic Analysis of Trehalose Alleviating Oxidative Stress in Myoblasts

Trehalose, a naturally occurring non-toxic disaccharide, has attracted considerable attention for its potential in alleviating oxidative stress in skeletal muscle. In this study, our aim was to elucidate the metabolic mechanisms underlying the protective effects of trehalose against hydrogen peroxide (H₂O₂)-induced oxidative stress in C2C12 myoblasts. Our results show that both trehalose treatment and pretreatment effectively alleviate the H₂O₂-induced decrease in cell viability, reduce intracellular reactive oxygen species (ROS), and attenuate lipid peroxidation. Furthermore, using NMR-based metabolomics analysis, we observed that trehalose treatment and pretreatment modulate the metabolic profile of myoblasts, specifically regulating oxidant metabolism and amino acid metabolism, contributing to their protective effects against oxidative stress. Importantly, our results reveal that trehalose treatment and pretreatment upregulate the expression levels of P62 and Nrf2 proteins, thereby activating the Nrf2-NQO1 axis and effectively reducing oxidative stress. These significant findings highlight the potential of trehalose supplementation as a promising and effective strategy for alleviating oxidative stress in skeletal muscle and provide valuable insights into its potential therapeutic applications.