RT Journal Article SR Electronic T1 Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.10.19.345686 DO 10.1101/2020.10.19.345686 A1 Geraldine Maier A1 Julien Delezie A1 Pål O. Westermark A1 Gesa Santos A1 Danilo Ritz A1 Christoph Handschin YR 2020 UL http://biorxiv.org/content/early/2020/10/19/2020.10.19.345686.abstract AB 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.HighlightsMaximal endurance performance is greater in the early morningTimed exercise differentially alters the muscle transcriptome and (phospho)-proteomeMorning exercise triggers energy provisioning and tissue regenerationEvening exercise activates stress-related and catabolic pathwaysTraining exerts poor Zeitgeber activity on the muscle and liver clocksCompeting Interest StatementThe authors have declared no competing interest.AbbreviationsAMPKAMP-activated protein kinaseAtf3activating transcription factor 3Bmal1brain and muscle ARNT (aryl hydrocarbon receptor nuclear translocator)-Like 1Ciartcircadian associated repressor of transcriptionClockcircadian locomotor output cycles kaputCry 1/2/3crypochrome1/2CtrlcontrolDAdaytime activityDbpalbumin D box-binding proteinGLUT4glucose transporter 4Hk2hexokinase 2LDlight-darkNr4a3nuclear receptor subfamily 4 group A member 3 / NOR-1Pdk4pyruvate dehydrogenase kinase 4Per1/2/3period 1/2/3Ppargc-1α / PGC-1αperoxisome proliferator-activated receptor γ coactivator 1αSPPskeleton photoperiodTbc1d1TBC1 domain family member 1ZTZeitgeber time