Caveolin-3 regulates slow oxidative myofiber formation in female mice

Caveolin-3 (Cav-3) plays a pivotal role in maintaining skeletal muscle mass and function. Mutations or deletions of Cav-3 can result in the development of various forms of myopathy, which affect the integrity and repair capacity of muscle fiber membranes. However, the potential effect of Cav-3 on myofiber type composition remains unclear. To investigate the effect of Cav-3 on muscle strength and running capacity, we examined the grip force test and the low/high-speed running test. Oxidative and glycolytic myofiber-related genes, proteins, and skeletal muscle fiber composition were measured to determine the role of the Cav-3 in oxidative myofiber formation. We report the impact of Cav-3 on enhancing muscle endurance performance in female mice, and the discovery of a new physiological function to increase the proportion of slow-twitch oxidative muscle fiber by analyzing the gastrocnemius and soleus. Skeletal muscle-specific ablation of Cav-3 in female mice increased oxidative myofiber-related gene expression and type I oxidative myofiber composition, with resultant improvements in endurance performance. In male mice, the absence of Cav-3 in skeletal muscle reduced in the expression of glycolytic fiber-related genes and proteins. This study identified Cav-3 as a regulator of slow-twitch oxidative muscle fiber formation acting on female mice, which may provide a potential target for improving muscle oxidative function.