Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel.
HP2 Laboratory, Inserm U1042, University Grenoble Alpes, Grenoble, France.
Cell Metab. 2019 Jul 2;30(1):78-91.e4. doi: 10.1016/j.cmet.2019.03.012. Epub 2019 Apr 18.
Physical performance relies on the concerted action of myriad responses, many of which are under circadian clock control. Little is known, however, regarding the time-dependent effect on exercise performance at the molecular level. We found that both mice and humans exhibit daytime variance in exercise capacity between the early and late part of their active phase. The daytime variance in mice was dependent on exercise intensity and relied on the circadian clock proteins PER1/2. High-throughput gene expression and metabolic profiling of skeletal muscle revealed metabolic pathways that are differently activated upon exercise in a daytime-dependent manner. Remarkably, we discovered that ZMP, an endogenous AMPK activator, is induced by exercise in a time-dependent manner to regulate key steps in glycolytic and fatty acid oxidation pathways and potentially enhance exercise capacity. Overall, we propose that time of day is a major modifier of exercise capacity and associated metabolic pathways.
体力表现依赖于无数反应的协同作用，其中许多反应受生物钟控制。然而，对于分子水平上运动表现的时间依赖性影响，我们知之甚少。我们发现，无论是在小鼠还是人类中，其活动期的早、晚两部分的运动能力都存在日间差异。小鼠的日间差异取决于运动强度，且依赖于生物钟蛋白 PER1/2。骨骼肌的高通量基因表达和代谢特征分析显示，代谢途径会以依赖于日间的方式在运动后被不同程度地激活。值得注意的是，我们发现 ZMP，一种内源性 AMPK 激活剂，会随时间的推移而被运动诱导，以调节糖酵解和脂肪酸氧化途径中的关键步骤，并可能增强运动能力。总的来说，我们提出，一天中的时间是运动能力和相关代谢途径的主要调节剂。
