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

SIMPLE SUMMARY: Obesity is a growing public health problem worldwide. It is a pathological state that degrades the proper functioning of skeletal muscle. Diazoxide treatment and exercise have been shown to generally improve muscle function. However, the effect that each of the different exercise intensities has when combined with diazoxide on the contraction capacity, resistance to fatigue and oxidative stress levels in rat skeletal muscle is unknown. Therefore, this work focused on analyzing which exercise intensity was more efficient in combination with diazoxide in improving muscle tissue and its metabolic capacities. The best results were obtained with low- and moderate-intensity exercise when combined with the drug. These results expected to open a window of time that allows the implementation of a constant and prolonged exercise protocol that completely reverses the harmful effects of obesity on muscle tissue and obesity itself. ABSTRACT: Obesity is a chronic disease that impairs skeletal muscle function, affects the ability to contract, and promotes the development of fatigue. For this reason, the study of treatments that seek to reduce the harmful effects of obesity on muscle tissue has been deepened. Diazoxide treatment and various exercise protocols have been proposed to protect skeletal muscle against oxidative stress and its effects. However, the intensity and duration of exercise combined with diazoxide that would obtain the best results for improving skeletal muscle function in obese rats is unknown. To this end, this study evaluated the effects of three different exercise intensities combined with diazoxide on contraction capacity, resistance to fatigue, markers of oxidative stress, lipid peroxidation, ROS, and glutathione redox status of skeletal muscle. The results showed that treatments with diazoxide and exercise at different intensities improved muscle contraction capacity by reducing oxidative stress during obesity, with the best results being obtained with low-intensity exercise in combination with diazoxide. Therefore, these results suggest that diazoxide and low-intensity exercise improve muscle function during obesity by decreasing oxidative stress with the same efficiency as a moderate-intensity exercise protocol.