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Cell Metab. 2019 Apr 11. pii: S1550-4131(19)30141-X. doi: 10.1016/j.cmet.2019.03.012. [Epub ahead of print]

Physiological and Molecular Dissection of Daily Variance in Exercise Capacity.

Author information

1
Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel.
2
HP2 Laboratory, Inserm U1042, University Grenoble Alpes, Grenoble, France.
3
Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: gad.asher@weizmann.ac.il.

Abstract

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.

KEYWORDS:

AICAR; ZMP; circadian rhythm; clocks; exercise; metabolism; metabolomics; mitochondria; skeletal muscle; transcriptomics

PMID:
31006590
DOI:
10.1016/j.cmet.2019.03.012

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