Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and zeitgeber activity of training in mouse muscle

KEY POINTS: Maximal endurance performance is greater in the early daytime. Timed exercise differentially alters the muscle transcriptome and (phospho)‐proteome. Early daytime exercise triggers energy provisioning and tissue regeneration. Early night‐time exercise activates stress‐related and catabolic pathways. Scheduled training has limited effects on the muscle and liver circadian clocks. ABSTRACT: Timed physical activity might potentiate the health benefits of training. The underlying signalling events triggered by exercise at different times of day are, however, poorly understood. Here, we found that time‐dependent variations in maximal treadmill exercise capacity of naïve mice were associated with energy stores, mostly hepatic glycogen levels. Importantly, running at different times of day resulted in a vastly different activation of signalling pathways, e.g. related to stress response, vesicular trafficking, repair and regeneration. Second, voluntary wheel running at the opposite phase of the dark, feeding period surprisingly revealed a minimal zeitgeber (i.e. phase‐shifting) effect of training on the muscle clock. This integrated study provides important insights into the circadian regulation of endurance performance and the control of the circadian clock by exercise. In future studies, these results could contribute to better understanding circadian aspects of training design in athletes and the application of chrono‐exercise‐based interventions in patients.