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

Abstract

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.

Comparative Effect of Three Different Exercise Intensities in Combination with Diazoxide on Contraction Capacity and Oxidative Stress of Skeletal Muscle in Obese Rats

“…ROS is one of the primary markers of oxidative stress, the excessive accumulation of these molecules is associated with structural and functional damage to cells. During obesity, there is excessive production of ROS [ 19 , 23 ]. There is a relationship between the amount of ROS produced at the systemic level and in the muscle, and the reduction in muscle contractility and appearance of fatigue [ 43 ].…”

“…It should be mentioned that this effect is more compatible when combined with low-intensity exercise. The decrease in lipid peroxidation during obesity is associated with the improvement in metabolic and functional capacities of the muscle and, above all, its capacity for contraction and fatigue resistance ( Figure 1 ) [ 23 ].…”

“…Glutathione is included in this system, whose synthesis can be altered by exercise, diet, and age [ 17 , 43 ]. In this study, it was possible to observe how oxidative stress increased as a consequence of obesity-induced skeletal muscle atrophy and vice versa and how, during this pathology, the antioxidant response is insufficient, which promotes the overproduction of ROS and the oxidation of lipids in the cells of the muscle fibers [ 6 , 23 , 47 ]. Our results showed that total glutathione and the GSH/GSSG ratio of the soleus and EDL muscle ( Figure 4 ) were decreased during obesity, suggesting that obesity interferes with the synthesis of this antioxidant, possibly because the ROS that are overproduced during this disease are related in the activation of signaling pathways that adversely affect glutathione synthesis such as NF-Kb, Sp1, E [ 11 , 23 , 50 ].…”

“…However, the response obtained from the exercise will depend on the intensity, duration and the type of exercise applied [ 16 ]; the exercise can be classified in different intensities according to the VO2 max and the heart rate that is obtained [ 22 ]. The exercise protocol applied, will be determine from the physiological and metabolic response obtained [ 23 ]. In the case of obesity, there is contradictory information about which exercise intensity would be most optimal to treat the pathology and its direct effects on the functioning of muscle tissue.…”

“…In the case of obesity, there is contradictory information about which exercise intensity would be most optimal to treat the pathology and its direct effects on the functioning of muscle tissue. Recent studies show similar effects between high-intensity interval training and continuous training of moderate intensity, but without making it clear which one is recommended to improve the functioning of muscle tissue during obesity [ 2 , 16 , 23 ].…”