ChREBP Is Dispensable for Myofiber Type-switch but Promotes Skeletal Muscle Regeneration

Muscle performance and fatigability are determined by the structural and metabolic properties of the specialized myofibers. Skeletal muscle demonstrates significant plasticity, with myofiber types and energy metabolic functions undergoing adaptive remodeling in response to physiological or pathophysiological stimuli. The transcription factor carbohydrate-responsive element-binding protein (ChREBP) is recognized as a crucial glucose-sensing regulator involved in glucose and lipid metabolism. However, However, the precise role of ChREBP in influencing myofiber composition and energy metabolism within muscle tissue remains ambiguous. Here, utilizing skeletal muscle-specific knockout mice, we demonstrated that ChREBP deletion did not substantially alter muscle fiber composition or metabolic function, nor did it play a role in skeletal muscle adaptive remodeling under hypoxic or high-fructose dietary conditions. Interestingly, the absence of ChREBP was associated with a modest enhancement in aerobic exercise capacity, although it markedly impaired lipid transport function and led to a reduction in triglyceride content. Furthermore, we observed that upregulation of ChREBP expression significantly increased the number of newly formed myofibers and their cross-sectional area. Taken together, this study elucidates the role of ChREBP in skeletal muscle and its adaptive remodeling, while also identifying a significant promotive function of ChREBP in the repair of skeletal muscle injuries.