ChREBP Is Dispensable for Myofiber Type Switch but Promotes Skeletal Muscle Regeneration

Area of Science:

• Molecular Biology
• Metabolic Regulation
• Skeletal Muscle Physiology

Background:

• Carbohydrate response element-binding protein (ChREBP) is a critical regulator of glucose and lipid metabolism.
• The precise functions of ChREBP in skeletal muscle are not fully understood.
• Investigating ChREBP's role is crucial for understanding muscle health and disease.

Purpose of the Study:

• To elucidate the role of ChREBP in skeletal muscle exercise capacity, energy metabolism, and adaptive remodeling.
• To determine ChREBP's involvement in skeletal muscle regeneration and repair.
• To explore ChREBP's influence on myogenic differentiation.

Main Methods:

• Generation of a skeletal muscle-specific ChREBP knockout mouse model.
• Assessment of exercise performance, energy metabolism, fiber composition, and injury repair.
• Utilized hypoxia and high-fructose diet models for adaptive remodeling studies.
• Employed C2C12 myoblasts and primary muscle satellite cells for in vitro differentiation assays.

Main Results:

• Skeletal muscle-specific ChREBP deletion did not alter myofiber composition, metabolic status, or adaptive remodeling under stress.
• ChREBP overexpression enhanced myogenic differentiation in vitro.
• ChREBP overexpression improved regeneration markers and myofiber formation post-injury in vivo.

Conclusions:

• ChREBP is largely dispensable for basal skeletal muscle homeostasis and stress-induced adaptive remodeling.
• This study reveals a novel role for ChREBP in promoting skeletal muscle damage repair and post-injury regeneration.