Table_1_Time-restricted feeding restores metabolic flexibility in adult mice with excess adiposity.xlsx

IntroductionObesity is prevalent with the adult population in the United States. Energy-dense diets and erratic eating behavior contribute to obesity. Time-restricted eating is a dietary strategy in humans that has been advanced to reduce the propensity for obesity. We hypothesized that time-restricted feeding (TRF) would improve metabolic flexibility and normalize metabolic function in adult mice with established excess adiposity.MethodsMale C57BL/6NHsd mice were initially fed a high-fat diet (HFD) for 12 weeks to establish excess body adiposity, while control mice were fed a normal diet. Then, the HFD-fed mice were assigned to two groups, either ad libitum HFD or TRF of the HFD in the dark phase (12 h) for another 12 weeks.Results and discussionEnergy intake and body fat mass were similar in TRF and HFD-fed mice. TRF restored rhythmic oscillations of respiratory exchange ratio (RER), which had been flattened by the HFD, with greater RER amplitude in the dark phase. Insulin sensitivity was improved and plasma cholesterol and hepatic triacylglycerol were decreased by TRF. When compared to HFD, TRF decreased transcription of circadian genes Per1 and Per2 and genes encoding lipid metabolism (Acaca, Fads1, Fads2, Fasn, Scd1, and Srebf1) in liver. Metabolomic analysis showed that TRF created a profile that was distinct from those of mice fed the control diet or HFD, particularly in altered amino acid profiles. These included aminoacyl-tRNA-biosynthesis, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, TRF improved metabolic function in adult mice with excess adiposity. This improvement was not through a reduction in body fat mass but through the restoration of metabolic flexibility.

引言肥胖在美国成年人中普遍存在。高能量密度饮食和不规律的饮食习惯是导致肥胖的重要因素。限时饮食是人类的一种饮食策略，旨在降低肥胖倾向。本研究假设限时喂养（TRF）能够改善成年小鼠的代谢灵活性并使其代谢功能恢复正常。方法将雄性C57BL/6NHsd小鼠首先喂以高脂肪饮食（HFD）12周，以建立超常的体脂，而对照组小鼠则喂以普通饮食。随后，HFD喂养的小鼠被分为两组，一组为自由摄食HFD，另一组在黑暗阶段（12小时）进行HFD的限时喂养，持续另外12周。结果与讨论限时喂养组与HFD喂养组的小鼠能量摄入和体脂质量相似。限时喂养恢复了由HFD导致的呼吸交换比（RER）的节律性波动，在黑暗阶段的RER振幅更大。限时喂养改善了胰岛素敏感性，并降低了血浆胆固醇和肝三酰甘油。与HFD相比，限时喂养降低了肝脏中昼夜节律基因Per1和Per2以及编码脂质代谢（Acaca、Fads1、Fads2、Fasn、Scd1和Srebf1）的基因的转录。代谢组学分析显示，限时喂养产生的特征与喂以对照组饮食或HFD的小鼠的特征明显不同，特别是在改变的氨基酸谱方面。这些包括氨基酸tRNA生物合成、谷胱甘肽代谢以及苯丙氨酸、酪氨酸和色氨酸生物合成途径。总之，限时喂养改善了超常体脂成年小鼠的代谢功能。这种改善并非通过减少体脂质量，而是通过恢复代谢灵活性来实现。