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

Abstract
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+Exe are associated with improved hepatic metabolism and decreased hepatic lipid accumulation. TRF combined with AE training increased fatty acid oxidation and decreased the lipogenic and gluconeogenic genes’ expression 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 signaling 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. This study performed TRF (8 h in the active phase), and TRF combined with AE (TRF+Exe) and evaluated the effects on insulin sensitivity and hepatic gene expressions involved in fatty acid oxidation, lipogenesis, and gluconeogenesis in male Swiss mice fed a high‐fat diet. As previous reports, we show that TRF alone (eating only between ZT16 and ZT0) 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 (VO2), carbon dioxide production (VCO2), and production of ketone bodies (β‐hydroxybutyrate). Also, TRF+Exe attenuated the negative effects of high‐fat diet feeding on insulin signaling pathway (IR, IRS, Akt), and led to increased fatty acid oxidation (Ppara, Cpt1a) as well as decreased gluconeogenic (Fbp1, Pck1, Pgc1a) and lipogenic (Srebp1c, Cd36) genes 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 glycemic homeostasis in young male Swiss mice. This article is protected by copyright. All rights reserved
Funding Information
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (124053/2019‐0)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (001)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (2019/00227‐1, 2018/20872‐6)