Sodium butyrate regulates proliferation of skeletal muscle satellite cells in Arbas cashmere goats: molecular mechanisms from an in vitro study

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 (MuSCs) in Arbas Cashmere Goats, an area that remains understudied. The present study demonstrates that NaB promotes the proliferation of MuSCs by coordinately activating the CSF1R-ERK1/2-RSK2 signaling axis and enhancing the acetylation levels at histone H3K9 and H3K27 sites. This finding provides new insights into the molecular mechanisms by which small-molecule compounds regulate skeletal muscle development and offers experimental evidence for understanding the regulatory basis of muscle development in the Arbas Cashmere Goat. This study systematically elucidated the multi-faceted molecular mechanisms by which NaB regulates proliferation in MuSCs of the Arbas Cashmere Goat by integrating in vitro experimental approaches, including RNA-seq, signaling pathway validation, molecular docking, and histone acetylation analysis. The results demonstrate that NaB synergistically promotes cell proliferation through a dual mechanism involving epigenetic modulation and signaling pathway activation: on one hand, it binds to and activates the CSF1R receptor, initiating the ERK1/2-RSK2 signaling axis; on the other hand, it inhibits histone deacetylase activity, specifically elevating the acetylation levels of H3K9 and H3K27. This work provides novel experimental evidence clarifying the molecular mechanisms by which short-chain fatty acids regulate muscle development and suggests potential targets for developing related nutritional intervention strategies.