Endurance Exercise and the Regulation of Skeletal Muscle Metabolism

Almost a half century ago, regular endurance exercise was shown to improve the capacity of skeletal muscle to oxidize substrates to produce ATP for muscle work. Since then, adaptations in skeletal muscle mRNA level were shown to happen with a single bout of exercise. Protein changes occur within days if daily endurance exercise continues. Some of the mRNA and protein changes cause increases in mitochondrial concentrations. One mitochondrial adaptation that occurs is an increase in fatty acid oxidation at a given absolute, submaximal workload. Mechanisms have been described as to how endurance training increases mitochondria. Importantly, Pgc-1α is a master regulator of mitochondrial biogenesis by increasing many mitochondrial proteins. However, not all adaptations to endurance training are associated with increased mitochondrial concentrations. Recent evidence suggests that the energetic demands of muscle contraction are by themselves stronger controllers of body weight and glucose control than is muscle mitochondrial content. Endurance exercise has also been shown to regulate the processes of mitochondrial fusion and fission. Mitophagy removes damaged mitochondria, a process that maintains mitochondrial quality. Skeletal muscle fibers are composed of different phenotypes, which are based on concentrations of mitochondria and various myosin heavy chain protein isoforms. Endurance training at physiological levels increases type IIa fiber type with increased mitochondria and type IIa myosin heavy chain. Endurance training also improves capacity of skeletal muscle blood flow. Endurance athletes possess enlarged arteries, which may also exhibit decreased wall thickness. VEGF is required for endurance training-induced increases in capillary-muscle fiber ratio and capillary density.