Abstract

Metabolic Associated Fatty Liver Disease (MAFLD) is a prevalent chronic condition with limited therapeutic options, making lifestyle interventions a primary strategy. This study investigated whether exercise, alone or with dietary modifications, mitigates HFD-induced alterations in rats of both sexes. The motor coordination, plasma glucose and irisin levels, oxidative stress and inflammatory biomarkers (catalase, superoxide dismutase, glutathione peroxidase, malondialdehyde and myeloperoxidase) in liver and muscle, and hepatic Nrf2, NF-kappa B, and UCP-2 expression were evaluated. Rats were fed a HFD for 3 months, followed by 2 months of interventions consisting of exercise and a shift to a standard diet (SD) or antioxidant-rich diet. Control and HFD groups received pellet and HFD, respectively, for the full 5 months. The results showed improvements in weight gain, motor performance, and antioxidant profiles in tissues when exercise was combined with dietary changes in both sexes. Exercise alone was enough to improve motor coordination in males. Plasma glucose and irisin recovered control values, especially when exercise was combined with a healthier diet in both sexes. Nrf2, NF-kappa B and UCP-2 expression, altered by the HFD, were also restored after interventions. Overall, the combination of exercise and an antioxidant-rich diet produced the most pronounced improvements across all parameters. In conclusion, combining exercise and a healthier diet, especially rich in antioxidants, led to marked improvements in motor function and plasma and tissue biomarkers with slight differences between females and males.