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橘皮苷通过靶向 AdipoR1 增加氧化肌纤维增强小鼠肌肉耐力和有氧代

泰然健康网
2024-12-27 16:08

Jinjie Li, Jiangtao Li, Amin Ullah, Xiaoyang Shi, Xinyuan Zhang, Zhenwei Cui, Quanjun Lyu, Guangning Kou

摘要

慢氧化肌纤维在提高肌肉耐力表现和维持机体能量平衡方面发挥着重要作用。然而，调节慢速氧化肌纤维比例的靶点和方法仍然未知。在这里，我们发现天然多甲氧基化黄酮橘皮素（TG）能显著激活慢速氧化肌纤维相关基因的表达并增加 I 型肌纤维的比例，从而改善小鼠的耐力表现和有氧代谢。蛋白质组学、分子动力学、细胞热转移试验（CETSA）和药物亲和力反应靶点稳定性（DARTS）研究发现，TG能直接与脂肪素受体1（AdipoR1）结合。通过使用敲除 AdipoR1 的 C2C12 细胞和肌肉特异性 AdipoR1 敲除小鼠，我们发现 TG 对慢速氧化肌纤维相关标志物表达的积极调节作用是由 AdipoR1 及其下游 AMPK/PGC-1α 通路介导的。总之，我们的数据揭示了 TG 是一种天然化合物，它能通过靶向 AdipoR1 信号通路调节慢速氧化肌纤维的特性。这些发现进一步揭示了 TG 在增加慢速氧化肌纤维比例和提高骨骼肌性能方面的新功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

摘要图片

Tangeretin Enhances Muscle Endurance and Aerobic Metabolism in Mice via Targeting AdipoR1 to Increase Oxidative Myofibers

Slow oxidative myofibers play an important role in improving muscle endurance performance and maintaining body energy homeostasis. However, the targets and means to regulate slow oxidative myofibers proportion remain unknown. Here, we show that tangeretin (TG), a natural polymethoxylated flavone, significantly activates slow oxidative myofibers-related gene expression and increases type I myofibers proportion, resulting in improved endurance performance and aerobic metabolism in mice. Proteomics, molecular dynamics, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) investigations revealed that TG can directly bind to adiponectin receptor 1 (AdipoR1). Using AdipoR1-knockdown C2C12 cells and muscle-specific AdipoR1-knockout mice, we found that the positive effect of TG on regulating slow oxidative myofiber related markers expression is mediated by AdipoR1 and its downstream AMPK/PGC-1α pathway. Together, our data uncover TG as a natural compound that regulates the identity of slow oxidative myofibers via targeting the AdipoR1 signaling pathway. These findings further unveil the new function of TG in increasing the proportion of slow oxidative myofibers and enhancing skeletal muscle performance.