Efeitos benéficos de jejum intermitente e treinamento intervalado de alta intensidade no fígado e músculo esquelético de camundongos obesos

Abstract

Obesity is commonly associated with nonalcoholic fatty liver disease (NAFLD) and skeletal muscle dysfunction. Intermittent fasting (IF) and high-intensity interval training (HIIT) are procedures that might mitigate the adverse effects of both alterations. Objective: The study aims to evaluate the effects of IF, HIIT, and their combination on NAFLD and skeletal muscle of diet-induced obese (DIO) mice. Methodology: Two groups of 3-month-old C57BL/6 male mice were fed for 16 weeks with a control (C) or high-fat (HF) diet. In the last 4 weeks, IF, HIIT, and IF/HIIT were implemented. Results: Obese HF animals showed liver and intramuscular fat accumulation with macro-, micro-vesicular steatosis (liver) and inflammatory infiltrate (liver/muscle). IF and HIIT reduced hepatic steatosis in the HF-derived groups. IF, HIIT and IF/HIIT were beneficial in glucose metabolism in groups derived from C and HF. Elevated levels of total cholesterol and triacylglycerols were observed in plasma and liver in the HF group compared with the C group, and were attenuated by IF, HIIT, and IF/HIIT. IF decreased adiponectin and increased leptin and insulin in the HF groups. HIIT benefited adiponectin and leptin. IF reduced hepatic gene expression of interleukin-6 (IL-6) in the C JI group, and IL-6 and PAI-1 in the HF group. The IF/HIIT group reduced IL-6, MCP-1 and PAI-1. IF and HIIT increased beta-oxidation. IF and HIIT reduced lipogenesis in HF-derived groups. HIIT increased calf muscles' contribution to body mass and reduced weight gain in HF HIIT than the HF group. Peak velocity was higher in C HIIT, C IF/HIIT, HF HIIT, and HF IF/HIIT than in C and HF, respectively. Both plasma insulin and blood glucose were reduced in the HF HIIT and HF IF/HIIT groups. Fndc5 and Irisin were higher in C HIIT, C IF/HIIT, HF HIIT, and HF IF/HIIT. Muscle Fgf21 was more elevated in HF HIIT and HF IF/HIIT compared to HF. In addition, NfKb and Tnfa were lower in HF/HIIT than HF. Compared to HF, Interleukins decreased in the HF JI, HF HIIT, and HF JI/HIIT groups. HIIT reduced ER stress markers in HF, HIIT, and HF JI/HIIT compared to HF. Conclusions: IF, HIIT and their combination provide a reduction in body mass, insulin resistance, hepatic steatosis/inflammation, lipogenesis in the liver and muscle, increase glucose tolerance and oxidation of fatty acids. IF is the main intervening factor that benefits the liver of obese mice. HIIT leads to a reduction in body mass and minimizes muscle depletion, increases glycemic control, Irisin-Fndc5 and peak velocity. In addition, alleviate muscle inflammation and ER stress. Thus, both strategies alone and combined can be effective tools to mitigate the harmful effects of a high-fat diet.