High-intensity interval training and moderate-intensity continuous training attenuate oxidative damage and promote myokine response in the skeletal muscle of ApoE KO mice on high-fat diet

The purpose of this study was to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the skeletal muscle in Apolipoprotein E knockout (ApoE KO) and wild-type (WT) C57BL/6J mice. ApoE KO mice fed with a high-fat diet were randomly allocated into: Control group without exercise (ApoE−/− CON), HIIT group (ApoE−/− HIIT), and MICT group (ApoE−/− MICT). Exercise endurance, blood lipid profile, muscle antioxidative capacity, and myokine production were measured after six weeks of interventions. ApoE−/− CON mice exhibited hyperlipidemia and increased oxidative stress, compared to the WT mice. HIIT and MICT reduced blood lipid levels, ROS production, and protein carbonyl content in the skeletal muscle, while it enhanced the GSH generation and potently promoted mRNA expression of genes involved in the production of irisin and BAIBA. Moreover, ApoE−/− HIIT mice had significantly lower plasma HDL-C content, mRNA expression of MyHC-IIx and Vegfa165 in EDL, and ROS level; but remarkably higher mRNA expression of Hadha in the skeletal muscle than those of ApoE−/− MICT mice. These results demonstrated that both exercise programs were effective for the ApoE KO mice by attenuating the oxidative damage and promoting the myokines response and production. In particular, HIIT was more beneficial to reduce the ROS level in the skeletal muscle

Effects of high intensity exercise in hypoxia on vascular function in mouse models

Cardiovascular diseases are the main cause of death globally with an estimated 18.6 million deaths worldwide in 2019. Atherosclerosis-induced endothelial dysfunction is an independent risk factor for cardiovascular diseases, and therefore one of the main targets in primary and secondary prevention. Exercise training is highly recommended by international guidelines for the prevention of cardiovascular diseases, but also as the gold standard treatment in some pathologies (i.e., lower extremity peripheral artery disease). Recently, evidence showed promising results from combining exercise training and hypoxia to potentiate the vascular dilator function observed with the same level of exercise in normoxia. However, the optimal characteristics of exercise that would induce an improvement of endothelial function and/or regression of atherosclerosis, remain unclear. This work first demonstrated that hypoxic exercise training improved endothelial function compared to the same training in normoxia in healthy mice. Then, we found that the combination of high-intensity exercise and hypoxia improved endothelial function more than low-intensity exercise training in hypoxia. These first two results indicate a potential application for high-intensity exercise in hypoxia as a novel therapeutic strategy to improve and/or preserve endothelial function. Endothelial function is known to be modulated by the nitric oxide pathway, and a dysfunction in the production and/or bioavailability of nitric oxide gives ground for the development of endothelial dysfunction. Therefore, we ultimately investigated the nitric oxide pathway and showed that rather than being modulated by an increased nitric oxide production, the improved endothelial function was secondary to a systemic shift in the pro-/antioxidant balance towards an antioxidant profile, impacting nitric oxide bioavailability. In conclusion, our work brought new perspective for the treatment of endothelial dysfunction and cardiovascular disease prevention. It also opens possibilities for testing this type of training on mouse models of cardiovascular diseases, in particular atherosclerosis and lower extremity peripheral artery disease. This will benefit patients and physicians looking to optimize physical activity prescription to prevent or treat cardiovascular diseases. -- Les maladies cardiovasculaires sont la première cause de mortalité dans le monde avec environ 18.6 millions de décès en 2019. La dysfonction endothéliale induite par l’athérosclérose est un facteur de risque indépendant des maladies cardiovasculaires, et est donc une des cibles principales des préventions primaires et secondaires. L’exercice physique est le traitement de référence pour certaines de ces pathologies selon les recommandations internationales. Récemment, l’exercice physique en hypoxie a montré des résultats prometteurs pour potentialiser la vasodilatation en comparaison avec le même type d’exercice en normoxie. Cependant, les caractéristiques optimales d’exercice permettant une amélioration de la fonction endothéliale et/ou une régression du développement de l’athérosclérose, demeures inconnues. Ce travail a tout d’abord démontré chez la souris saine qu’un exercice en hypoxie améliore davantage la fonction endothéliale que le même entraînement en normoxie ; et ce, d’autant plus avec un exercice à haute intensité qu’à intensité modérée. Ces premiers résultats suggèrent un potentiel effet thérapeutique de l’exercice de haute intensité en hypoxie pour améliorer et/ou préserver la fonction endothéliale. D’un point de vue mécanistique, le bénéfice observé serait le résultat non pas d’une augmentation de la production de monoxyde d’azote, mais d’une orientation de la balance pro- /antioxydante au niveau systémique vers le profil antioxydant, augmentant la biodisponibilité du monoxyde d’azote. En conclusion, notre travail amène de nouvelles perspectives pour le traitement de la dysfonction endothéliale et la prévention des maladies cardiovasculaires. Il ouvre également la possibilité de tester ces types d’entraînement sur des modèles murins de pathologies humaines, en particulier d’athérosclérose et de la maladie artérielle périphérique. Ce travail apporte de nouvelles pistes aux patients et médecins cherchant à optimiser la prescription d’exercice pour prévenir traiter les maladies cardiovasculaires