Muscle Rev-Erb Controls Time-Dependent Adaptations to Chronic Exercise in Mice

Authors

Jidong Liu
Fang Xiao
Abhinav Choubey
Udhaya Kumar S
Yanxiang Wang
Sungguan Hong
Tingting Yang
Husniye Gul Otlu
Ege Sanem Oturmaz
Emanuele Loro
Yuxiang Sun
Pradip Saha
Tejvir S Khurana
Li Chen
Xinguo Hou
Zheng Sun

Language

English

Publication Date

7-1-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-60520-y

PMID

40593528

PMCID

PMC12216418

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal that Rev-erb suppresses fatty acid oxidation and promotes carbohydrate metabolism before sleep. Thus, the muscle-autonomous clock, not feeding or locomotor behaviors, dictates diurnal variations of muscle functions and time-dependent adaptations to training, which has broad implications in metabolic disorders and sports medicine as Rev-erb agonists are exercise mimetics or enhancers.

Keywords

Animals, Male, Physical Conditioning, Animal, Nuclear Receptor Subfamily 1, Group D, Member 1, Muscle, Skeletal, Adaptation, Physiological, Mice, Mice, Knockout, Circadian Rhythm, Mice, Inbred C57BL, Muscle Contraction, Circadian Clocks, Fatty Acids, Repressor Proteins, Receptors, Cytoplasmic and Nuclear, Fat metabolism, Metabolic syndrome, Translational research

Published Open-Access

yes

Recommended Citation

Liu, Jidong; Xiao, Fang; Choubey, Abhinav; et al., "Muscle Rev-Erb Controls Time-Dependent Adaptations to Chronic Exercise in Mice" (2025). Huffington Center on Aging Staff Publications. 72.
https://digitalcommons.library.tmc.edu/aging_research/72