Time‐restricted feeding combined with exercise improves hepatic and glycaemic metabolism in obese mice: A sex‐dependent study

Erratic feeding patterns, such as those experienced by shift workers, can exacerbate obesity and metabolic-associated fatty liver disease (MAFLD). Both nutritional factors and sexual dimorphism influence the progression of MAFLD. Time-restricted feeding (TRF) has emerged as a promising strategy to mitigate the effects of obesity, supported by evidence of its benefits for metabolic disorders like MAFLD. Regular physical exercise is also recommended as a non-pharmacological approach to combat obesity and its related conditions. Both TRF and exercise independently show promise in improving metabolic health, weight management and glycaemic control. Thus, combining these approaches may offer a more effective strategy against obesity and MAFLD. In this study, male and female C57BL/6J mice were subjected to an 8-week obesity induction protocol, followed by TRF (16/8) or TRF combined with aerobic exercise. The results showed that TRF, even during the inactive phase of the mice, had positive effects on weight loss, adiposity, glycaemic homeostasis, insulin sensitivity, liver lipid composition, hepatic fat accumulation and the reduction of lipogenic and inflammatory genes in the liver. The combination of TRF with aerobic exercise provided additional benefits, including improved regulation of hepatic triglycerides and respiratory exchange ratio (RER) in males, enhanced fasting glucose levels in females and reduced Fatp4 gene expression in both sexes. Aerobic exercise performance also improved in both sexes, with males achieving superior results. Notably, the combination of TRF with aerobic exercise provided greater metabolic benefits, with sex-specific differences observed in metabolic responses. KEY POINTS: Eight weeks of western diet induced obesity, an impaired glucose homeostasis and increased hepatic fat accumulation in male and female C57BL/6J mice. Time-restricted feeding (TRF) 16/8 in the active phase and TRF combined with aerobic exercise reduced weight gain and metabolic disorders in C57BL/6J male and female mice fed a western diet. TRF when combined with aerobic exercise displayed more pronounced improvements in the hepatic metabolism. TRF when combined with aerobic exercise improved liver triglycerides and respiratory exchange ratio in males, fasting glucose in females and decreased lipogenic gene Fatp4 expression in both males and females.