Effect of moderate exercise on skeletal muscle mitochondrial function and dynamics in obese Zucker rats

Abstract

Obesity and metabolic syndrome are related to a significant reduction in mitochondrial quality. Current evidence suggests that both conditions promote an unbalance between fusion and fission, the main events of mitochondrial dynamics and this is associated with alterations in mitochondrial function, mainly in highly energetic tissues such as skeletal muscle. In the treatment of obesity and metabolic disorders, the various adaptations resulting from moderate-intensity physical exercise stand out, which are considered to be regulated by AMPK. This project aimed to evaluate modifications in gene and protein expression of the main regulators of mitochondrial dynamics and, using confocal microscopy, determine changes in mitochondrial function through the evaluation of membrane potential and distribution changes in the main mitochondrial subpopulations in a murine model of obesity after chronic moderate exercise. 12 weeks old male Zucker obese rats were randomly divided into a sedentary obese group and an exercise obese group (n=4 per group). The exercise consisted of 4 weeks of swimming training for 60min/5days a week. After 48 hours of the last exercise bout, animals were euthanized and both gastrocnemius muscles were isolated. A significant increase in fission was evidenced by changes in phosphorylation of Drp1 and AMPK. Subsarcolemmal mitochondria showed a more organized network in comparison with the sedentary group while there was no change in the intermyofibrillar region. An increase in fission regulated by AMPK might be segregating damaged mitochondria and enhancing its removal while activating mitochondrial biogenesis to ensure restoration of mitochondrial mass by generating a healthier population in the subsarcolemmal region.