Time-restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high-fat diet.

KEY POINTS: Time-restricted feeding (TRF, in which energy intake is restricted to 8 h/day during the dark phase) alone or combined with aerobic exercise (AE) training can prevent weight gain and metabolic disorders in Swiss mice fed a high-fat diet. The benefits of TRF combined with AE are associated with improved hepatic metabolism and decreased hepatic lipid accumulation. TRF combined with AE training increased fatty acid oxidation and decreased expression of lipogenic and gluconeogenic genes in the liver of young male Swiss mice. TRF combined with AE training attenuated the detrimental effects of high-fat diet feeding on the insulin signalling pathway in the liver. ABSTRACT: Time-restricted feeding (TRF) or physical exercise have been shown to be efficient in the prevention and treatment of metabolic disorders; however, the additive effects of TRF combined with aerobic exercise (AE) training on liver metabolism have not been widely explored. In this study TRF (8 h in the active phase) and TRF combined with AE (TRF+Exe) were compared in male Swiss mice fed a high-fat diet, with evaluation of the effects on insulin sensitivity and expression of hepatic genes involved in fatty acid oxidation, lipogenesis and gluconeogenesis. As in previous reports, we show that TRF alone (eating only between zeitgeber time 16 and 0) was sufficient to reduce weight and adiposity gain, increase fatty acid oxidation and decrease lipogenesis genes in the liver. In addition, we show that mice of the TRF+Exe group showed additional adaptations such as increased oxygen consumption ( V̇O2${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ ), carbon dioxide production ( V̇CO2${\dot V_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ ) and production of ketone bodies (ß-hydroxybutyrate). Also, TRF+Exe attenuated the negative effects of high-fat diet feeding on the insulin signalling pathway (insulin receptor, insulin receptor substrate, Akt), and led to increased fatty acid oxidation (Ppara, Cpt1a) and decreased gluconeogenic (Fbp1, Pck1, Pgc1a) and lipogenic (Srebp1c, Cd36) gene expression in the liver. These molecular results were accompanied by increased glucose metabolism, lower serum triglycerides and reduced hepatic lipid content in the TRF+Exe group. The data presented in this study show that TRF alone has benefits but TRF+Exe has additive benefits and can mitigate the harmful effects of consuming a high-fat diet on body adiposity, liver metabolism and glycaemic homeostasis in young male Swiss mice.