Inducible skeletal muscle-specific p53 deletion alleviates high-fat diet-induced insulin resistance by modulating mitochondria-associated membrane in obese mice.

ABSTRACT: p53 has been implicated in metabolic regulation, but its role in obesity-induced skeletal muscle insulin resistance remains incompletely understood. This study aimed to determine the functional contribution of skeletal muscle p53 to insulin resistance and mitochondrial dysfunction, particularly in the context of obesity. We demonstrate that inducible, skeletal muscle-specific deletion of p53 (iMp53 KO) significantly improves insulin sensitivity in high-fat diet (HFD)-induced obese mice, with no effect in chow-fed controls. This metabolic improvement was accompanied by enhanced mitochondrial respiration and membrane potential, as well as reduced mitochondrial calcium overload in palmitate-treated C2C12 myotubes. Electron microscopy and immunoblotting revealed a marked reduction in mitochond

SUBMITTER: Park S 

PROVIDER: S-EPMC12540039 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature