Physiological and molecular dissection of daily variance in exercise capacity

Physical performance relies on the concerted action of myriad responses, many of which are under circadian clock control. Little is known, however, regarding the time-dependent effect on exercise performance at the molecular level. We found that both mice and humans exhibit day-time variance in exercise capacity between the early and late part of their active phase. The day-time variance in mice was dependent on exercise intensity and relied on the circadian clock proteins PER1/2. High throughput gene expression and metabolic profiling of skeletal muscle revealed metabolic pathways that are differently activated upon exercise in a day-time dependent manner. Remarkably, we discovered that ZMP, an endogenous AMPK activator, is induced by exercise in a time-dependent manner to regulate key steps in glycolytic and fatty acid oxidation pathways and potentially enhance exercise capacity. Overall, we propose that time of the day is a major modifier of exercise capacity and associated metabolic pathways. basal, high intensity and moderate intensity runnig protocol at ZT14 and ZT22 in gastrocnemius muscle in C57B6 mice