Ferulic acid mediates Mongolian horse skeletal muscle fiber remodeling through PDK1.

Ferulic acid (FA), a natural antioxidant and major active component in Angelica sinensis, has beneficial effects on skeletal muscle health; however, its role in modulating muscle fiber type composition Mongolian horse remains unclear. In this study, we found that FA promotes the proliferation of Mongolian horse skeletal muscle satellite cell (MuSCs), upregulates the expression of fast-twitch muscle marker genes (e.g., MYH2), and downregulates the expression of slow-twitch markers (e.g., MYH7). RNA-seq revealed that FA activates the HIF-1 signaling pathway, significantly increasing PDK1 expression. Molecular docking analysis demonstrated that FA directly binds to PDK1, thereby facilitating the switch from slow- to fast-twitch muscle fibers. Functional assays using PDK1 knockdown and overexpression confirmed its regulatory role in muscle fiber type specification. Furthermore, RNA-seq and protein-protein interaction (PPI) network analyses indicated that PDK1 interacts with LDHA and IL6 to influence glycolysis and muscle contraction-related pathways. A feeding experiment further validated that FA promotes the transition toward fast-twitch muscle fibers in vivo. Collectively, our findings uncover a novel mechanism by which FA regulates muscle fiber type transformation through the HIF-1/PDK1 signaling axis.