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

摘要

慢氧化肌纖維在提高肌肉耐力表現(xiàn)和維持機(jī)體能量平衡方面發(fā)揮著重要作用。然而，調(diào)節(jié)慢速氧化肌纖維比例的靶點(diǎn)和方法仍然未知。在這里，我們發(fā)現(xiàn)天然多甲氧基化黃酮橘皮素（TG）能顯著激活慢速氧化肌纖維相關(guān)基因的表達(dá)并增加 I 型肌纖維的比例，從而改善小鼠的耐力表現(xiàn)和有氧代謝。蛋白質(zhì)組學(xué)、分子動(dòng)力學(xué)、細(xì)胞熱轉(zhuǎn)移試驗(yàn)（CETSA）和藥物親和力反應(yīng)靶點(diǎn)穩(wěn)定性（DARTS）研究發(fā)現(xiàn)，TG能直接與脂肪素受體1（AdipoR1）結(jié)合。通過(guò)使用敲除 AdipoR1 的 C2C12 細(xì)胞和肌肉特異性 AdipoR1 敲除小鼠，我們發(fā)現(xiàn) TG 對(duì)慢速氧化肌纖維相關(guān)標(biāo)志物表達(dá)的積極調(diào)節(jié)作用是由 AdipoR1 及其下游 AMPK/PGC-1α 通路介導(dǎo)的?？傊?，我們的數(shù)據(jù)揭示了 TG 是一種天然化合物，它能通過(guò)靶向 AdipoR1 信號(hào)通路調(diào)節(jié)慢速氧化肌纖維的特性。這些發(fā)現(xiàn)進(jìn)一步揭示了 TG 在增加慢速氧化肌纖維比例和提高骨骼肌性能方面的新功能。

本文章由計(jì)算機(jī)程序翻譯，如有差異，請(qǐng)以英文原文為準(zhǔn)。

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.

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網(wǎng)址: 橘皮苷通過(guò)靶向 AdipoR1 增加氧化肌纖維增強(qiáng)小鼠肌肉耐力和有氧代 http://m.u1s5d6.cn/newsview853135.html