Gong Wendian, Ding Wenqi, Bou Tugeqin, Shi Lin, Lin Yanan, Shi Xiaoyuan, Wu Huize, Li Zheng, Dugarjaviin Manglai, Bai Dongyi
College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China; Equine Research Center, College of Animal Science, Hohhot, China.
College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China; Equine Research Center, College of Animal Science, Hohhot, China.
Genomics. 2025 Sep;117(5):111086. doi: 10.1016/j.ygeno.2025.111086. Epub 2025 Jul 17.
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.
阿魏酸（FA）是当归中的一种天然抗氧化剂和主要活性成分，对骨骼肌健康有益；然而，其在调节蒙古马肌纤维类型组成方面的作用仍不清楚。在本研究中，我们发现FA促进蒙古马骨骼肌卫星细胞（MuSCs）的增殖，上调快肌标记基因（如MYH2）的表达，并下调慢肌标记基因（如MYH7）的表达。RNA测序显示FA激活HIF-1信号通路，显著增加PDK1的表达。分子对接分析表明FA直接与PDK1结合，从而促进慢肌纤维向快肌纤维的转变。使用PDK1敲低和过表达的功能实验证实了其在肌纤维类型特化中的调节作用。此外，RNA测序和蛋白质-蛋白质相互作用（PPI）网络分析表明，PDK1与LDHA和IL6相互作用，影响糖酵解和肌肉收缩相关途径。一项喂养实验进一步证实，FA在体内促进向快肌纤维的转变。总的来说，我们的研究结果揭示了一种新的机制，即FA通过HIF-1/PDK1信号轴调节肌纤维类型转变。
