The Regulatory Effects of Sodium Butyrate on Skeletal Muscle Satellite Cell Proliferation and Its Molecular Mechanisms in Arbas Cashmere Goats

Abstract Background The Arbas Cashmere Goat of Inner Mongolia is renowned for its meat, characterized by a firm and fine texture, high nutritional value, evenly distributed fat, and a distinctive flavor profile that combines the unique taste of goat meat with the tenderness of mutton. During the growth and development of cashmere goats, skeletal muscle development serves as a critical biological foundation determining production performance and meat quality, directly impacting the economic efficiency of animal husbandry. In recent years, research into the molecular mechanisms underlying skeletal muscle growth and development has advanced significantly. It has become increasingly clear that short-chain fatty acids (SCFAs), microbial metabolites derived from the gut microbiota, act as natural small-molecule compounds regulating muscle homeostasis via the "gut-muscle axis". Among these SCFAs, butyrate stands out as a crucial mediator molecule for deciphering the interaction mechanisms between the microbiome and muscle biology, owing to its unique epigenetic regulatory capabilities and signaling pathway activation properties. However, the specific regulatory mechanisms of butyrate in the skeletal muscle of Arbas Cashmere Goats remain poorly understood. Therefore, this study aims to investigate the regulatory mechanism of sodium butyrate (NaB) on the growth and development of skeletal muscle satellite cells in Arbas Cashmere Goats, an area that remains understudied. Results This study revealed that NaB promotes the proliferation of MuSCs by jointly activating the ERK1/2-RSK2 signaling axis through CSF1R and elevated acetylation modifications of H3K9ac and H3K27ac. These findings provide new insights into the molecular mechanisms by which small-molecule compounds regulate skeletal muscle development and offer experimental evidence for understanding the regulatory mechanisms of muscle development in Arbas Cashmere Goats. Conclusions By integrating transcriptomic sequencing, signaling pathway validation experiments, molecular docking, and histone acetylation assays, this study systematically deciphered the multidimensional molecular mechanisms through which NaB regulates the proliferation of MuSCs in Arbas Cashmere Goats. We revealed a dual-action mode involving epigenetic regulation and signaling pathway activation. Our results demonstrate that NaB promotes cell proliferation via a multi-target mechanism, co-activating ERK1/2 through CSF1R and elevated H3K9ac/H3K27ac acetylation modifications. These findings provide novel molecular targets and a theoretical basis for developing short-chain fatty acid-based strategies to regulate muscle development.