Antunes Gabriel Calheiros, Cunha Camila Venturini Ayres, Oharomari Leandro Kansuke, Vieira Renan Fudoli Lins, Fanti Maura, Rios Thaiane da Silva, Conceição de Mattis Luciana Renata, Azevêdo Macêdo Ana Paula, da Silva Adelino Sanchez Ramos, Ropelle Eduardo Rochete, Cintra Dennys Esper, Pauli José Rodrigo
Laboratory of Molecular Biology of Exercise, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
Laboratory of Nutritional Genomics, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
J Physiol. 2025 Aug 19. doi: 10.1113/JP287681.
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.
不规律的进食模式，如轮班工作者所经历的那样，会加剧肥胖和代谢相关脂肪性肝病（MAFLD）。营养因素和性别差异都会影响MAFLD的进展。限时进食（TRF）已成为一种有前景的减轻肥胖影响的策略，有证据表明其对MAFLD等代谢紊乱有益。定期体育锻炼也被推荐为对抗肥胖及其相关病症的非药物方法。TRF和锻炼各自在改善代谢健康、体重管理和血糖控制方面都显示出前景。因此，将这些方法结合起来可能提供一种对抗肥胖和MAFLD更有效的策略。在本研究中，将雄性和雌性C57BL/6J小鼠进行为期8周的肥胖诱导方案，随后进行TRF（16/8）或TRF联合有氧运动。结果表明，TRF即使在小鼠的非活动期，对体重减轻、肥胖、血糖稳态、胰岛素敏感性、肝脏脂质组成、肝脏脂肪积累以及肝脏中脂肪生成和炎症基因的减少都有积极影响。TRF与有氧运动相结合带来了额外的益处，包括改善雄性肝脏甘油三酯和呼吸交换率（RER）的调节、提高雌性空腹血糖水平以及降低两性的Fatp4基因表达。两性的有氧运动表现也都有所改善，雄性取得了更优异的结果。值得注意的是，TRF与有氧运动相结合带来了更大的代谢益处，在代谢反应中观察到了性别特异性差异。要点：八周的西式饮食诱导雄性和雌性C57BL/6J小鼠肥胖、葡萄糖稳态受损和肝脏脂肪积累增加。在活跃期进行16/8限时进食（TRF）以及TRF联合有氧运动可减轻喂食西式饮食的C57BL/6J雄性和雌性小鼠的体重增加和代谢紊乱。TRF与有氧运动相结合在肝脏代谢方面显示出更显著的改善。TRF与有氧运动相结合改善了雄性的肝脏甘油三酯和呼吸交换率、雌性的空腹血糖，并降低了雄性和雌性的脂肪生成基因Fatp4表达。
