Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
J Endocrinol. 2021 Jan;248(1):75-86. doi: 10.1530/JOE-20-0404.
Time-restricted feeding (TRF) initiated early during the dark phase prevents the metabolic consequences of a high-fat diet in rodent models. However, the metabolic consequences of delaying the initiation of TRF, akin to breakfast skipping in humans, is unclear. We assigned 8-week-old male C57BL/6J mice (n = 192) to chow or high-fat diet ad libitum (AL) for 4 weeks, before randomization to continue AL or 10 h of TRF, initiated at lights off (TRFe) or 4-h after lights off (TRFd) for a further 8 weeks. Oral glucose tolerance tests (1 g/kg), metabolic monitoring and body composition by echoMRI were performed, and tissues were collected at six time points. TRF reduced weight and fat mass vs AL, with a greater reduction in TRFe vs TRFd. TRF improved glucose tolerance and protected mice from high-fat diet-induced hepatosteatosis vs AL, with no difference between TRFe and TRFd. TRF increased the amplitude of Bmal1, Cry1, Per2, Nampt, and Nocturnin mRNA levels in liver. A phase delay in Bmal1, Cry1, Per2, Reverbα, Nampt, NAD, Sirt1, and Nocturnin was observed in TRFd. Thus, delaying TRF limited the weight benefit and induced a phase delay in the hepatic clock, but improved metabolic health. Allowing more flexibility in when TRF is initiated may increase the translational potential of this dietary approach in humans.
限时喂养（TRF）在黑暗期早期开始可以防止高脂肪饮食在啮齿动物模型中的代谢后果。然而，延迟 TRF 开始的代谢后果，类似于人类的不吃早餐，目前还不清楚。我们将 8 周龄雄性 C57BL/6J 小鼠（n = 192）分为随意进食正常饮食（AL）或高脂肪饮食（AL）4 周，然后随机分为继续 AL 或 10 小时限时喂养（TRFe）或在熄灯后 4 小时（TRFd）开始进一步限时喂养 8 周。进行口服葡萄糖耐量试验（1 g/kg）、代谢监测和 EchoMRI 体成分分析，并在六个时间点采集组织。TRF 可减轻体重和脂肪量，与 TRFe 相比，TRFd 的减轻效果更大。TRF 可改善葡萄糖耐量，并防止高脂肪饮食引起的肝脂肪变性，与 TRFe 和 TRFd 相比无差异。TRF 增加了肝脏中 Bmal1、Cry1、Per2、Nampt 和 Nocturnin mRNA 水平的振幅。在 TRFd 中观察到 Bmal1、Cry1、Per2、Reverbα、Nampt、NAD、Sirt1 和 Nocturnin 的相位延迟。因此，延迟 TRF 限制了体重获益，并诱导了肝脏时钟的相位延迟，但改善了代谢健康。允许在何时开始 TRF 更具灵活性，可能会增加这种饮食方法在人类中的转化潜力。
