Tangeretin Enhances Muscle Endurance and Aerobic Metabolism in Mice via Targeting AdipoR1 to Increase Oxidative Myofibers,Journal of Agricultural and Food Chemistry

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Tangeretin Enhances Muscle Endurance and Aerobic Metabolism in Mice via Targeting AdipoR1 to Increase Oxidative Myofibers
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-11 , DOI: 10.1021/acs.jafc.3c09386
Jinjie Li ₁ , Jiangtao Li ₁ , Amin Ullah ₂ , Xiaoyang Shi ₁ , Xinyuan Zhang ₁ , Zhenwei Cui ₁ , Quanjun Lyu ₂ , Guangning Kou _{1,

2}

Affiliation

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.

中文翻译：

橘皮素通过靶向 AdipoR1 增加氧化肌纤维来增强小鼠的肌肉耐力和有氧代谢

慢氧化肌纤维在提高肌肉耐力表现和维持身体能量稳态方面发挥着重要作用。然而，调节慢氧化肌纤维比例的目标和方法仍然未知。在这里，我们发现橘皮素（TG）是一种天然多甲氧基黄酮，可显着激活慢氧化肌纤维相关基因表达并增加 I 型肌纤维比例，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、细胞热位移测定 (CETSA) 和药物亲和力响应靶稳定性 (DARTS) 研究表明，TG 可以直接与脂联素受体 1 (AdipoR1) 结合。使用AdipoR1敲除的C2C12细胞和肌肉特异性AdipoR1敲除小鼠，我们发现TG对调节慢氧化肌纤维相关标记物表达的积极作用是由AdipoR1及其下游AMPK/PGC-1α途径介导的。总之，我们的数据揭示了 TG 作为一种天然化合物，可通过靶向 AdipoR1 信号通路来调节慢氧化肌纤维的特性。这些发现进一步揭示了TG在增加慢氧化肌纤维比例、增强骨骼肌性能方面的新功能。

更新日期：2024-07-11

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