Molecular control of endurance training adaptation in male mouse skeletal muscle

Abstract

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. Although morphological changes in endurance-trained muscles are well described, the molecular underpinnings of training adaptation are poorly understood. We therefore aimed to elucidate the molecular signature of muscles of trained male mice and unravel the training status-dependent responses to an acute bout of exercise. Our results reveal that, even though at baseline an unexpectedly low number of genes define the trained muscle, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part associated with epigenetic modifications. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor-γ coactivator 1α are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that underpins muscle plasticity in training.

Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training

“…We performed transcriptomic analysis of the gastrocnemius muscle of the control and exercise trained mice, with and without BMAL1. Analysis of the muscle from vehicle control and trained mice identified 142 DEGs after training which is consistent with prior studies [3,36]. Within those DEGs, 67 were upregulated, and 75 were downregulated after training, Figure 3A.…”

“…These outcomes suggest that the well-defined molecular responses to exercise training in skeletal muscle requires BMAL1 and/or a functional circadian clock mechanism, but in its absence requires a far larger network of genes to elicit adaptations. Our findings have similarities to recent work demonstrating the contribution of muscle specific Ppargc1a to the exercise training response [36]. This is not surprising as it has been shown that Ppargc1a is a clock output gene in skeletal muscle.…”

“…While similar, we detected an shared training response of only 2% between wildtype and muscle specific BMAL1 KO muscle. This suggests that exercise training works with the circadian clock either directly or in collaboration with clock output genes, such as Ppargc1a , to regulate the molecular adaptations to exercise training [36].…”

Orientin Promotes Antioxidant Capacity, Mitochondrial Biogenesis, and Fiber Transformation in Skeletal Muscles through the AMPK Pathway

“…PGC-1α plays a crucial role in determining muscle fiber type. 42 Mitochondria regulate energy generation, metabolic activities, and cellular signaling and are of paramount importance in maintaining overall cellular health. Considering this, mitochondrial impairment becomes a precipitating factor in the onset of various diseases including hepatic disorders, diabetes mellitus, and dementia.…”

“…PGC-1α plays a crucial role in determining muscle fiber type . Mitochondria regulate energy generation, metabolic activities, and cellular signaling and are of paramount importance in maintaining overall cellular health.…”