Clock proteins and training modify exercise capacity in a daytime-dependent manner

Abstract

Exercise and circadian biology are closely intertwined with physiology and metabolism, yet the functional interaction between circadian clocks and exercise capacity is only partially characterized. Here, we tested different clock mutant mouse models to examine the effect of the circadian clock and clock proteins, namely PERIODs and BMAL1, on exercise capacity. We found that daytime variance in endurance exercise capacity is circadian clock controlled. Unlike wild-type mice, which outperform in the late compared with the early part of their active phase, PERIODs- and BMAL1-null mice do not show daytime variance in exercise capacity. It appears that BMAL1 impairs and PERIODs enhance exercise capacity in a daytime-dependent manner. An analysis of liver and muscle glycogen stores as well as muscle lipid utilization suggested that these daytime effects mostly relate to liver glycogen levels and correspond to the animals’ feeding behavior. Furthermore, given that exercise capacity responds to training, we tested the effect of training at different times of the day and found that training in the late compared with the early part of the active phase improves exercise performance. Overall, our findings suggest that clock proteins shape exercise capacity in a daytime-dependent manner through changes in liver glycogen levels, likely due to their effect on animals’ feeding behavior.

Endogenous circadian temperature rhythms relate to adolescents’ daytime physical activity

“…Chronobiology and circadian rhythms have gained accumulating interest in healthcare; specifically their interactions with other processes that govern metabolism and whole-body physiology ( Burki, 2017 ). Exercise biology, including physical activity (PA) intensity, similarly explains mechanisms relating to overall health and metabolism ( Adamovich et al, 2021 ), thus, both PA and circadian rhythms are of interest from a public health perspective.…”

Daily running enhances molecular and physiological circadian rhythms in skeletal muscle

“…Type I fibers have a lower maximum sarcoplasmic reticulum Ca2 + -ATPase activity and, therefore, female skeletal muscle metabolism is more suited to resynthesizing ATP from oxidative phosphorylation during exercise [ 64 ]. Notably, another study recently reported that female mice have greater exercise capacity at ZT22 than they have at ZT14, using a different exercise test that preferentially measures endurance exercise capacity as revealed by depletion of circulating glucose [ 65 ].…”

“…Here, we demonstrate that voluntary running wheel activity consolidated in the early nighttime active phase led to increased running endurance regardless of the time of day, but enhanced maximal running speed only later in the night. Several circadian clock components influence muscle function and/or exercise capacities, including CRYs, PERs, FBXL21, and BMAL1 [ 6 , 10 , [14] , [15] , [16] , [17] , 28 , 65 , [72] , [73] , [74] , [75] , [76] ]. Notably, CRYs are phosphorylated by AMPK [ 77 ] and repress the transcription factors HIF1α [ 32 , 33 ] and PPARδ [ 17 ], each of which are established effectors of exercise-induced remodeling.…”

Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP)

“…Additional candidate genes were identified in the muscle of unselected control mice controlled by exercise (Clock, Ncam1, Fgfr4, and Hbegf). For these candidates, specific roles have been suggested with respect to metabolic adaptation [ 41 ], muscle innervation [ 42 ], training responses [ 43 ], or muscle cell differentiation [ 44 ]. It is possible that decades of selection under avoidance of inbreeding have enriched multiple mechanisms related to superior running performance in DUhTP mice, which might also warrant separate studies in the future.…”