Vieira Renan Fudoli Lins, Muñoz Vitor Rosetto, Junqueira Rafael Lima, de Oliveira Fellipe, Gaspar Rafael Calais, Nakandakari Susana Castelo Branco Ramos, Costa Suleyma de Oliveira, Torsoni Marcio Alberto, da Silva Adelino S R, Cintra Dennys Esper, de Moura Leandro Pereira, Ropelle Eduardo Rochete, Zaghloul Iman, Mekary Rania A, Pauli José Rodrigo
Laboratory of Molecular Biology of Exercise (LaBMEx), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
Laboratory of Nutritional Genomics (LabGeN), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
J Physiol. 2022 Feb;600(4):797-813. doi: 10.1113/JP280820. Epub 2021 Jan 26.
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.
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 ( ), carbon dioxide production ( ) and production of ketone bodies (β-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.
限时进食（TRF，即仅在黑暗期将能量摄入限制在每天8小时）单独或与有氧运动（AE）训练相结合，可防止高脂饮食喂养的瑞士小鼠体重增加和代谢紊乱。TRF与AE相结合的益处与改善肝脏代谢和减少肝脏脂质积累有关。TRF与AE训练相结合可增加年轻雄性瑞士小鼠肝脏中的脂肪酸氧化，并降低生脂和糖异生基因的表达。TRF与AE训练相结合减弱了高脂饮食对肝脏胰岛素信号通路的有害影响。
限时进食（TRF）或体育锻炼已被证明在预防和治疗代谢紊乱方面有效；然而，TRF与有氧运动（AE）训练相结合对肝脏代谢的附加作用尚未得到广泛研究。在本研究中，对高脂饮食喂养的雄性瑞士小鼠比较了TRF（活跃期8小时）和TRF与AE相结合（TRF+Exe）的情况，并评估了其对胰岛素敏感性以及参与脂肪酸氧化、脂肪生成和糖异生的肝脏基因表达的影响。正如之前的报道，我们发现单独的TRF（仅在授时因子时间16至0之间进食）足以减轻体重和脂肪增加，增加脂肪酸氧化并降低肝脏中的脂肪生成基因。此外，我们发现TRF+Exe组的小鼠表现出额外的适应性变化，如耗氧量增加、二氧化碳产生增加和酮体（β-羟基丁酸）生成增加。此外，TRF+Exe减弱了高脂饮食对胰岛素信号通路（胰岛素受体、胰岛素受体底物、Akt）的负面影响，并导致肝脏中脂肪酸氧化增加（Ppara、Cpt1a）以及糖异生（Fbp1、Pck1、Pgc1a）和脂肪生成（Srebp1c、Cd36）基因表达降低。这些分子水平的结果伴随着TRF+Exe组葡萄糖代谢增加、血清甘油三酯降低和肝脏脂质含量减少。本研究中的数据表明，单独的TRF有益处，但TRF+Exe具有附加益处，并且可以减轻高脂饮食对年轻雄性瑞士小鼠身体肥胖、肝脏代谢和血糖稳态的有害影响。
