Daytime-restricted feeding enhances running endurance without prior exercise in mice

Physical endurance and energy conservation are essential for survival in the wild. However, it remains unknown whether and how meal timing regulates physical endurance and muscle diurnal rhythms. Here, we show that day/sleep time-restricted feeding (DRF) enhances running endurance by 100% throughout the circadian cycle in both male and female mice, compared to either ad libitum feeding or night/wake time-restricted feeding. Ablation of the circadian clock in the whole body or the muscle abolished the exercise regulatory effect of DRF. Multi-omics analysis revealed that DRF robustly entrains diurnal rhythms of a mitochondrial oxidative metabolism-centric network, compared to night/wake time-restricted feeding. Remarkably, muscle-specific knockdown of the myocyte lipid droplet protein perilipin-5 completely mimics DRF in enhancing endurance, enhancing oxidative bioenergetics and outputting rhythmicity to circulating energy substrates, including acylcarnitine. Together, our work identifies a potent dietary regimen to enhance running endurance without prior exercise, as well as providing a multi-omics atlas of muscle circadian biology regulated by meal timing. Time-restricted feeding in the resting period is a potent dietary regimen to enhance running endurance in mice, by synchronizing rhythms of perilipin-5 in muscle tissues through involvement of the circadian clock.

Automated summary

Meal timing, specifically day/sleep time-restricted feeding, enhances running endurance and regulates muscle diurnal rhythms in mice. The circadian clock and a mitochondrial oxidative metabolism-centric network play key roles in mediating the effects of meal timing on physical endurance. Knockdown of the myocyte lipid droplet protein perilipin-5 in muscle tissues mimics the effects of day/sleep time-restricted feeding.