Molecular control of endurance training adaptation in mouse skeletal muscle

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. While morphological changes in endurance-trained muscles are well-described, the molecular underpinnings of training adaptation are poorly understood. We aimed at defining the molecular signature of a trained muscle and unraveling the training statusdependent responses to an acute bout of exercise. Our results reveal that even though at baseline, the transcriptomes of trained and untrained muscles are very similar, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part mediated by epigenetic modifications. Second, proteomic changes were elicited by different transcriptional modalities. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor {gamma} coactivator 1 (PGC-1) are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that defines muscle plasticity in training. HIGHLIGHTSO_LIVery few persistent transcriptional events define the trained muscle. C_LIO_LIThe training status determines the acute exercise response. C_LIO_LIEpigenetic changes shape the transcriptional specification of trained muscle. C_LIO_LIAbsence of the key regulator PGC-1 causes suboptimal training adaptations. C_LI