橘皮素通过AdipoR1-Caveolin3-APPL1通路促进骨骼肌Ⅰ型肌纤维转化作用及其机制研究

骨骼肌Ⅰ型肌纤维含有丰富的毛细血管与线粒体，是肌肉健康研究的突破点。团队前期研究发现柑橘多甲氧基黄酮提取物能够提高小鼠运动耐力，通过筛选发现其单体成分五甲氧基黄酮橘皮素具有增加肌肉线粒体生物发生的功能，提示橘皮素可能具有调控Ⅰ型肌纤维转化的作用。结合新近实验结果，本项目提出橘皮素通过AdipoR1-Caveolin3-APPL1轴调控Ⅰ型肌纤维转化的研究假设。本项目拟通过体内实验、肌肉组织离体实验以及体外实验，研究橘皮素补充对骨骼肌Ⅰ型肌纤维含量的影响，明确橘皮素在肌肉纤维类型转化中的调控作用；通过研究橘皮素对AdipoR1-Caveolin3-APPL1信号轴活化状态的影响，阐明该通路在骨骼肌纤维类型转化中发挥的作用及其作为橘皮素调控Ⅰ型肌纤维转化的潜在机制。本项目将为Ⅰ型肌纤维的营养补充提供新的干预手段，为Ⅰ型肌纤维相关疾病的防治提供新的干预靶点与调控途径。

Type Ⅰ myofiber containing a large number of myoglobins and mitochondria is a breakthrough point in research field of muscle health. Our previous study showed that citrus polymethoxyflavonoid extract can enhance exercise endurance in mice. Through screening, we found that its monomer component pentamethoxyflavones tangeretin has the function which increases skeletal muscle mitochondrial biogenesis, implying that tangeretin may regulate the conversion of skeletal muscle fibers. Based on our recent results, this project propose a hypothesis that tangeretin could promote type Ⅰ myofibers transition via AdipoR1-Caveolin3-APPL1 axis. In this study, the effects of tangeretin supplementation on promoting the conversion of Ⅰ myofibers were studied through in vivo, ex vivo and vitro models to clarify the regulatory role of tangeretin in muscle fiber type transition. By studying the effect of tangeretin on activating AdipoR1-Caveolin3-APPL1 signal axis, the role of this pathway in skeletal muscle fiber type transition and its potential mechanism as tangeretin regulating type I muscle fiber transition were clarified. This research will provide a new method for the nutritional supplementation of type Ⅰ myofiber, and supply a new target and mechanism for the prevention and treatment of type Ⅰ myofiber related diseases.