Circadian rhythms across mammalian tissues are coordinated by a master clock in the suprachiasmatic nucleus (SCN) that is principally entrained by light-dark cycles. Prior investigations have shown, however, that time-restricted feeding (TRF)—daily alternation of fasting and food availability—synchronizes peripheral clocks independent of the light-dark cycle and of the SCN. This has led to the idea that downstream peripheral clocks are entrained indirectly by food intake rhythms. However, TRF is not a normal eating pattern, and it imposes non-physiologic long fasts that rodents do not typically experience. Therefore, we tested whether normal feeding patterns can phase-shift or entrain peripheral tissues by measuring circadian rhythms of the liver, kidney, and submandibular gland in mPer2Luc mice under different food schedules. We employed home cage feeders to first measure ad libitum food intake and then to dispense 20-mg pellets on a schedule mimicking that pattern. In both conditions, PER2::LUC bioluminescence peaked during the night as expected. Surprisingly, shifting the scheduled feeding by 12 h advanced peripheral clocks by only 0–3 h, much less than predicted from TRF protocols. To isolate the effects of feeding from the light-dark cycle, clock phase was then measured in mice acclimated to scheduled feeding over the course of 3 months in constant darkness. In these conditions, peripheral clock phases were better predicted by the rest-activity cycle than by the food schedule, contrary to expectation based on TRF studies. At the end of both experiments, mice were exposed to a modified TRF with food provided in eight equally sized meals over 12 h. In the light-dark cycle, this advanced the phase of the liver and kidney, though less so than in TRF with ad libitum access; in darkness, this entrained the liver and kidney but had little effect on the submandibular gland or the rest-activity cycle. These data suggest that natural feeding patterns can only weakly affect circadian clocks. Instead, in normally feeding mice, the central pacemaker in the brain may set the phase of peripheral organs via pathways that are independent of feeding behavior.

中文翻译：

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天然食物的摄入方式对周围生物钟几乎没有同步作用

跨哺乳动物组织的昼夜节律由视交叉上核（SCN）中的主时钟协调，该主时钟主要由明暗循环带动。但是，先前的研究表明，限时喂食（TRF）–每天禁食和食物供应量的交替–使外围时钟同步，与明暗周期和SCN无关。这导致了一个想法，即下游外围时钟被进食节律间接夹带。但是，TRF不是正常的饮食方式，它会强加啮齿动物通常不会经历的非生理性禁食。因此，我们通过测量在不同食物安排下的mPer2Luc小鼠的肝脏，肾脏和下颌下腺的昼夜节律，测试了正常的喂养方式是否可以相移或夹带周围组织。我们使用了笼式喂食器，首先测量随意采食的食物，然后按照模仿该模式的时间表分配20毫克的颗粒。在两种情况下，PER2 :: LUC生物发光均在夜间达到了预期的峰值。令人惊讶的是，将排定的进给时间提前了12小时，将外围时钟提前了0–3小时，远低于TRF协议的预测。为了从光暗周期中分离出进食的影响，然后在恒定的黑暗中，在3个月的过程中，在适应计划进食的小鼠中测量时钟相位。在这种情况下，与其他饮食习惯相比，通过休息活动周期可以更好地预测周围的时钟相位，而不是通过饮食安排来预测。在两个实验结束时，将小鼠暴露于改良的TRF中，并在12小时内以八次均等大小的餐食提供食物。在明暗循环中，尽管没有随意进入的TRF相比，肝脏和肾脏的阶段有所进展。在黑暗中，这会夹带肝脏和肾脏，但对下颌下腺或休息活动周期影响很小。这些数据表明，自然的喂养方式只能对生物钟产生微弱的影响。取而代之的是，在正常喂养的小鼠中，大脑中的中央起搏器可能会通过与喂养行为无关的途径来设定周围器官的相位。