Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Timed physical activity might potentiate the health benefits of training. The underlying signaling events triggered by exercise at different times of the 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 the day resulted in a vastly different activation of signaling 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 minimal Zeitgeber (i.e., synchronizing) activity of training. This integrated study provides important insights into the circadian regulation of endurance performance and the control of the circadian clock by exercise. These results are of high importance to understand circadian aspects of training design in athletes and the application of chrono-exercise-based interventions in patients. Highlights ### Competing Interest Statement The authors have declared no competing interest. * Abbreviations : AMPK : AMP-activated protein kinase Atf3 : activating transcription factor 3 Bmal1 : brain and muscle ARNT (aryl hydrocarbon receptor nuclear translocator)-Like 1 Ciart : circadian associated repressor of transcription Clock : circadian locomotor output cycles kaput Cry 1/2/3 : crypochrome1/2 Ctrl : control DA : daytime activity Dbp : albumin D box-binding protein GLUT4 : glucose transporter 4 Hk2 : hexokinase 2 LD : light-dark Nr4a3 : nuclear receptor subfamily 4 group A member 3 / NOR-1 Pdk4 : pyruvate dehydrogenase kinase 4 Per1/2/3 : period 1/2/3 Ppargc-1α / PGC-1α : peroxisome proliferator-activated receptor γ coactivator 1α SPP : skeleton photoperiod Tbc1d1 : TBC1 domain family member 1 ZT : Zeitgeber time