Effects of time-restricted feeding and physical exercise on obesity and metabolic disorders in mice subjected to sleep deprivation and a high-fat diet

Abstract

Obesity is a major health issue, with diverse consequences including the exacerbated deposition of fat in the liver and reduction in skeletal muscle mass, which consequently contributes to the development of metabolic disorders such as hyperglycemia and the emergence of cardiovascular diseases, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In this scenario, multiple factors certainly interact, creating an obesogenic environment. Some factors are determining, including changes in the work cycle (shiftwork), inadequate nutrition, and physical inactivity. On the other hand, strategies such as time-restricted feeding (TRF) or physical exercise are efficient in preventing and treating metabolic disorders linked to obesity. However, the additive effects of TRF combined with aerobic and resistance exercise training (combined training, CT) on hyperglycemia, muscle mass, inflammation, and hepatic metabolism in a shiftwork model and feeding a high-fat diet have not been widely explored. In this study TRA (12 h light cycle) and TRF combined with CT (TRF+Exe) will be compared in male Swiss mice fed a high-fat diet and subjected to a sleep deprivation model (shiftwork), with the evaluation of the effects on hyperglycemia and insulin sensitivity, expression of genes and proteins related to hypertrophy and glucose uptake in skeletal muscle, and hepatic metabolic processes (oxidation and lipogenesis) and analysis of inflammatory markers. In addition, energy expenditure, locomotor activity, and mitochondrial function will be analyzed. Performance assessments will also be performed by completing the study experiments. We speculate that the combined intervention (TRF+CT) is capable of alleviating the impacts of obesity on health and, therefore, that the actions are complementary, resulting in preventive effects against metabolic, skeletal muscle, and liver disorders induced by the shiftwork model (deprivation sleep) and feeding with a high-fat diet.