Erk3 deletion drives oxidative adaptations in skeletal muscle

Skeletal muscle plays a central role in whole-body energy expenditure and metabolic homeostasis, and improving its mitochondrial function and oxidative fiber profile is considered an effective strategy to counteract diet-induced metabolic impairments, although the molecular regulators of these adaptations are not yet fully understood. Erk3 has been implicated in myotube differentiation and in skeletal muscle adaptations to aerobic exercise; however, its potential role in skeletal muscle during diet-induced metabolic dysfunction remains to be determined. Methods In this study, we used mice with striated muscle-specific Erk3 deletion alongside in vitro cultured myotubes, integrating metabolic phenotyping, indirect calorimetry, multi-omics profiling, and analyses of muscle morphology and fiber-type composition.