Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Cells. 2024 Jun 20;13(12):1069. doi: 10.3390/cells13121069.
Resveratrol is a polyphenol known to have metabolic as well as circadian effects. However, there is little information regarding the metabolic and circadian effect of resveratrol on muscle cells. We sought to investigate the metabolic impact of resveratrol throughout the circadian cycle to clarify the associated signaling pathways. C2C12 myotubes were incubated with resveratrol in the presence of increasing concentrations of glucose, and metabolic and clock proteins were measured for 24 h. Resveratrol led to SIRT1, AMPK and PP2A activation. Myotubes treated with increasing glucose concentrations showed higher activation of the mTOR signaling pathway. However, resveratrol did not activate the mTOR signaling pathway, except for P70S6K and S6. In accordance with the reduced mTOR activity, resveratrol led to advanced circadian rhythms and reduced levels of pBMAL1 and CRY1. Resveratrol increased myogenin expression and advanced its rhythms. In conclusion, resveratrol activates the SIRT1-AMPK-PP2A axis, advances circadian rhythms and induces muscle development.
白藜芦醇是一种众所周知的具有代谢和昼夜节律作用的多酚。然而，关于白藜芦醇对肌肉细胞的代谢和昼夜节律作用的信息很少。我们试图在整个昼夜节律周期内研究白藜芦醇的代谢影响，以阐明相关的信号通路。在存在葡萄糖浓度逐渐增加的情况下，将 C2C12 肌管与白藜芦醇孵育，并在 24 小时内测量代谢和时钟蛋白。白藜芦醇导致 SIRT1、AMPK 和 PP2A 激活。用逐渐增加的葡萄糖浓度处理的肌管显示 mTOR 信号通路的更高激活。然而，白藜芦醇除了 P70S6K 和 S6 之外，并没有激活 mTOR 信号通路。与降低的 mTOR 活性一致，白藜芦醇导致更先进的昼夜节律和 pBMAL1 和 CRY1 的水平降低。白藜芦醇增加肌生成素的表达并使其节律提前。总之，白藜芦醇激活 SIRT1-AMPK-PP2A 轴，提前昼夜节律并诱导肌肉发育。
