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.

The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms

“…As a detailed description of how pro-oxidants induce such adaptations is beyond the scope of this review, we refer interested readers to a review by Gomez-Gabrera [ 65 ]. These endogenous coping mechanisms increase the tissue’s ability to cope with oxidative stress/damage [ 66 , 67 ]. Hence, physical training has the potential to induce oxidative stress and underlying chemical alterations that are linked to beneficial health outcomes (i.e., oxidative eustress) (for a review, see [ 68 ]).…”

Sport Performance and Manual Therapies: A Review on the Effects on Mitochondrial, Sarcoplasmatic and Ca2+ Flux Response

“…Muscular hypertrophy is regulated by different cellular pathways, in particular, by the anabolic PI3K–Akt–mTOR pathway [ 48 ]. Despite these different consequences, both aerobic and anaerobic exercises share several metabolic pathways and, as a result, even anaerobic training may increase the PGC-1α synthesis [ 49 ].…”

Anti-Inflammatory and Antioxidant Effects of Dietary Supplementation and Lifestyle Factors

“…The aim of this issue was to collect and synthesize pertinent literature from original investigations to review articles surrounding these areas, and to provide evidence-based source to enhance our understanding. Collectively, this Special Issue includes 12 empirical investigations that covered multiple aspects of inflammation and oxidative stress from the perspectives of specific nutrients, such as alpha-lipoic acid [ 3 ] and sulforaphane [ 4 ], and 6 distinct review articles that aimed to consolidate and summarize our understanding of diverse contexts, such as exercising within hypoxia [ 5 ], and the influence of diet and dietary antioxidants on mood and depression [ 6 ]. In a fundamental review for this issue, Taherkhani and colleagues [ 7 ] provide an overview of the mechanistic effects of physical activity on inflammatory cytokines and oxidative stress and how dietary antioxidant consumption can modulate these responses.…”

“…In this regard, it is important to be mindful of the negative consequences of inflammation and oxidative stress; however, they can play important roles in themselves in triggering adaptive signaling processes after, for example, exercise and/or nutritional intake. In this regard, Li and colleagues [ 5 ] provide a complementary insight into relevant molecular mechanisms that govern adaptations to a popular exercise modality, high-intensity interval training, and hypoxia exposure. High-intensity interval training is a popular training modality for healthy individuals but, counterintuitively in some individuals’ minds, is also gaining momentum as a training modality for diseased conditions [ 8 ].…”