Effects of metabolic stress and exercise on skeletal muscle structure and function

Abstract

Introduction Obesity and diabetes induce structural and metabolic disturbances in insulin-sensitive tissues. Furthermore, physical exercise is one of the most prescribed lifestyle modifications to counteract these disturbances. However, comparisons of metabolic effects between different exercise modalities in an obesity context are scarce and require further investigation. Aims To investigate the metabolic effect of two isocaloric training programs: moderate-intensity endurance (END) or high intensity interval training (HIIT), in a mouse model of diet-induced obesity using a preventive and a treatment approach; and to investigate the effect of long-term diabetes and obesity on the skeletal muscle extracellular matrix (ECM). Methods Three different animal experiments were designed to achieve the aims of this thesis. 1) 72 male C57BL/6 mice were fed with standard CHOW or high-fat diet (HFD) for 10 weeks; simultaneously they underwent one of two different isocaloric exercise programs, constant-moderate (END) or high-intensity interval training (HIIT) for the same 10 weeks. 2) 72 male C57BL/6 mice were fed with standard CHOW or HFD for 10 weeks; then they underwent END or HIIT for another 10 weeks. In the third experiment, 51 male C57BL/6 mice were fed with standard CHOW or HFD for 15 weeks; then in a subset of each dietary group diabetes was induced. Subsequently, dietary intervention was continued for another 15 weeks. Results From a preventive perspective, END and HIIT induced similar metabolic benefits in HFD mice, however, only END normalized glucose metabolism markers. In already obese and insulin resistant mice, HIIT induced a better metabolic effect in quadriceps (skeletal muscle) and subcutaneous adipose tissue, whereas specific benefits were seen in the liver after END. Regarding the muscle ECM, diabetes induced a fibrotic profile. In contrast, HFD alone induced a dysregulation in ECM regulators. Conclusions Different exercise prescriptions exert differential metabolic benefits in high-fat fed mice. END induced greater desirable metabolic benefits in a preventive context, whereas HIIT appears to give greater efficacy in already obese and insulin-resistant mice. Future research should aim to explore the mechanisms behind these differential effects of exercise.