Modulation of exercise-induced gene expression in human skeletal muscle by exercise intensity, training status and short-term endurance training

摘要

A single bout of exercise generates a robust, but transient, increase in mRNA abundance for a multitude of genes, which is thought to contribute to the recovery from and adaptation to exercise. Adaptation to exercise training is mediated by the accumulation of pulses of elevatedudmRNA after individual exercise bout within a training program, leading to longer term increases in protein abundance that culminate in physiological adaptations. Several signalling pathways involving cytoplasmic protein kinases, transcription factors and their coregulators areudrecognised as regulators by which activation transduces physiological stimuli into transcriptional adaptations.udThis thesis examined the modulation of gene expression in human skeletal muscle under varying physiological conditions, including divergent exercise intensities, untrained and trained muscle, and short-term endurance training.udCompared to low intensity isocaloric exercise (400 kcal, 40%VO2peak), a single bout of high intensity exercise (80% VO2peak) resulted in greater activation of the signalling kinases AMPK and CaMKII, coincident with a larger increase in mRNA abundance of PGC-1α and FOXO1A during recovery. A single bout exercise induced an increase in PGC-1α. FOXO1A, and PDK4 mRNA abundance in both untrained and trained muscle. This may form part of a transcriptional response that contributes to exercise-induced alterations in skeletal muscle metabolism such as glucose sparing and increased fat oxidation during recovery from exercise. Fourteen consecutive days of endurance training resulted in the accumulation of mRNA and corresponding protein for some (ERRα, COXIV), but not all (FOXO1A, PDK4), reportedly acuteudexercise-responsive genes. This suggests that certain genes are involved in the restoration of homeostasis after acute exercise, whereas others are involved in adaptation to regular exercise. Our results illustrate the well-described phenomenology of skeletal muscle plasticity and suggest that transcript level adjustments underlie modulation of skeletal muscle metabolism and phenotype by regular exercise.