The Molecular Adaptive Responses of Skeletal Muscle to High-Intensity Exercise/Training and Hypoxia

Abstract

High-intensity exercise/training, especially interval exercise/training, has gained popularity in recent years. Hypoxic training was introduced to elite athletes half a century ago and has recently been adopted by the general public. In the current review, we have summarised the molecular adaptive responses of skeletal muscle to high-intensity exercise/training, focusing on mitochondrial biogenesis, angiogenesis, and muscle fibre composition. The literature suggests that (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) PGC-1α, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1-alpha (HIF1-α) might be the main mediators of skeletal muscle adaptations to high-intensity exercises in hypoxia. Exercise is known to be anti-inflammatory, while the effects of hypoxia on inflammatory signalling are more complex. The anti-inflammatory effects of a single session of exercise might result from the release of anti-inflammatory myokines and other cytokines, as well as the downregulation of Toll-like receptor signalling, while training-induced anti-inflammatory effects may be due to reductions in abdominal and visceral fat (which are main sources of pro-inflammatory cytokines). Hypoxia can lead to inflammation, and inflammation can result in tissue hypoxia. However, the hypoxic factor HIF1-α is essential for preventing excessive inflammation. Disease-induced hypoxia is related to an upregulation of inflammatory signalling, but the effects of exercise-induced hypoxia on inflammation are less conclusive. The effects of high-intensity exercise under hypoxia on skeletal muscle molecular adaptations and inflammatory signalling have not been fully explored and are worth investigating in future studies. Understanding these effects will lead to a more comprehensive scientific basis for maximising the benefits of high-intensity exercise.

Keywords: high-intensity exercise; hypoxia; inflammatory signalling; skeletal muscle; training.

Figure 1

A speculative model for the molecular adaptive responses of skeletal muscle to both high-intensity exercise/training and hypoxia. Both exercise/training and hypoxia induce a range of adaptations, including an upregulation in angiogenesis and mitochondrial biogenesis and a shift in the skeletal muscle fibre type. Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF) play important roles in the regulation of the adaptive response to both high-intensity exercise/training and hypoxia within skeletal muscle.

Figure 2

A speculative model for the inflammatory responses to high-intensity exercise/training and hypoxia. Exercise/Training exhibits anti-inflammatory effects via the induction of anti-inflammatory cytokines and downregulating toll-like receptor (TLR) signalling. Hypoxia is pro-inflammatory and mediates the upregulation of TLR signalling. HIF-1α is important in regulating the inflammatory response to high-intensity exercise/training and hypoxia.