Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle

Abstract

Skeletal muscle exhibits superb plasticity in response to changes in functional demands. Chronic increases of skeletal muscle contractile activity, such as endurance exercise, lead to a variety of physiological and biochemical adaptations in skeletal muscle, including mitochondrial biogenesis, angiogenesis, and fiber type transformation. These adaptive changes are the basis for the improvement of physical performance and other health benefits. This review focuses on recent findings in genetically engineered animal models designed to elucidate the mechanisms and functions of various signal transduction pathways and gene expression programs in exercise-induced skeletal muscle adaptations.

Fig. 1.

Schematic presentation of the current understanding of the signaling and molecular mechanisms underlying endurance exercise-induced adaptation in skeletal muscle. The figure depicts an adult skeletal muscle fiber with neuromuscular junction, capillary and intracellular metabolic (subsarcolemmal and intermyofibrillar mitochondria) and contractile (myofibrils) apparatuses. Muscle contractile activity, or endurance exercise, activates various protein phosphatase and kinases, which in turn regulate transcriptional factors, coactivators, and repressors in the control of contractile protein genes in fiber type transformation, mitochondrial genes in mitochondrial biogenesis, and angiogenic growth factor genes in angiogenesis. Solid lines between the regulatory factors depict the findings that have been confirmed by targeted gene deletion studies in animal models, while dashed lines depict findings by transgenic approaches in animal models, but not yet by targeted gene deletion studies. The relationships that have been confirmed by gene deletion studies not present in animal models in response to endurance exercise training are not depicted in this figure, such as the regulation of fiber type transformation by peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and mitochondrial biogenesis by CaMKIV. ERRα, estrogen-related receptor α; NFAT, nuclear factor of activated T-cells; NRF1/2, nuclear respiratory factor 1/2; MEF2, myocyte enhancer factor 2; CnA, calcineurin A.