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Transcriptional control of training adaptation in skeletal muscle

ABSTRACT: Skeletal muscle has an enormous plastic potential and adapts to various stimuli such as mechanical stress, nutrients and hormones. While morphological changes observed in endurance trained muscles are well described, the molecular underpinnings of training adaptation is poorly understood. Therefore, the aim of our study was to define the molecular signature of a trained muscle and unravel the transcriptional responses of untrained and trained muscles to an acute bout of endurance exercise. Our results reveal that even though at baseline, the transcriptome of trained and untrained muscles is very similar, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively. Therefore, we provide novel insights into the complex molecular processes that are induced in response to exercise in a temporal- and training status-dependent manner. In addition, our study reveals that the epigenetic landscape contributes to the transcriptional memory of a trained muscle.

ORGANISM(S): Mus musculus

PROVIDER: GSE221210 | GEO | 2023/08/04

REPOSITORIES: GEO

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Project description:Age-related declines in cardiorespiratory fitness and physical function are mitigated by regular endurance exercise in older adults. This may be due, in part, to changes in the transcriptional program of skeletal muscle following repeated bouts of exercise. However, the impact of chronic exercise training on the transcriptional response to an acute bout of endurance exercise has not been clearly determined. Here, we characterized baseline differences in muscle transcriptome and exercise-induced response in older adults who were active/endurance trained or sedentary. RNA-sequencing was performed on vastus lateralis biopsy specimens obtained before, immediately after, and 3 h following a bout of endurance exercise (40 min of cycling at 60%–70% of heart rate reserve). Using a recently developed bioinformatics approach, we found that transcript signatures related to type I myofibers, mitochondria, and endothelial cells were higher in active/endurance-trained adults and were associated with key phenotypic features including V̇o2peak, ATPmax, and muscle fiber proportion. Immune cell signatures were elevated in the sedentary group and linked to visceral and intermuscular adipose tissue mass. Following acute exercise, we observed distinct temporal transcriptional signatures that were largely similar among groups. Enrichment analysis revealed catabolic processes were uniquely enriched in the sedentary group at the 3-h postexercise timepoint. In summary, this study revealed key transcriptional signatures that distinguished active and sedentary adults, which were associated with difference in oxidative capacity and depot-specific adiposity. The acute response signatures were consistent with beneficial effects of endurance exercise to improve muscle health in older adults irrespective of exercise history and adiposity.

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