Natural food intake patterns have little synchronizing effect on peripheral circadian clocks.
Natural food intake patterns have little synchronizing effect on peripheral circadian clocks.
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DOI：
10.1186/s12915-020-00872-7
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发表时间：
2020-11-06
期刊：
影响因子：
5.4
通讯作者：
Butler MP
中科院分区：
文献类型：
--
作者：
Xie X;Kukino A;Calcagno HE;Berman AM;Garner JP;Butler MP
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周期携带。然而，先前的研究表明，限时喂养（TRF）-禁食和食物供应的每日交替-破坏了独立于明暗周期和SCN的外围时钟。这导致了这样一种想法，即下游外围时钟间接地被食物摄入节律所携带。然而，TRF不是一种正常的进食模式，它会造成啮齿动物通常不会经历的非生理性长时间禁食。因此，我们测试是否正常的喂养模式可以相移或夹带外周组织，通过测量昼夜节律的肝脏，肾脏，和下颌下腺mPer 2Luc小鼠在不同的食物时间表。我们采用笼式饲养器，首先测量自由采食量，然后按照模拟该模式的时间表分配20 mg颗粒。在这两种情况下，PER 2：：LUC生物发光在夜间达到峰值。令人惊讶的是，将预定喂养时间提前12小时，仅提前0-3小时，远低于TRF方案的预测。为了将喂食的影响与光-暗循环分离，然后在恒定黑暗中在3个月的过程中在适应预定喂食的小鼠中测量时钟相位。在这些条件下，外周时钟相位更好地预测的休息活动周期比食物时间表，相反的预期基于TRF研究。在两个实验结束时，小鼠暴露于改良的TRF，在12小时内以8次相同大小的膳食提供食物。在明-暗周期中，这提前了肝脏和肾脏的相位，尽管不如自由进入的TRF;在黑暗中，这夹带了肝脏和肾脏，但对颌下腺或休息-活动周期几乎没有影响。这些数据表明，自然喂养模式只能微弱地影响生物钟。相反，在正常进食的小鼠中，大脑中的中央起搏器可能通过独立于进食行为的通路来设定外周器官的相位。
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.
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影响因子：
4.6
作者：
Kuroda, Hiroaki;Tahara, Yu;Saito, Keisuke;Ohnishi, Nobuaki;Kubo, Yuji;Seo, Yasuhiro;Otsuka, Makiko;Fuse, Yuta;Ohura, Yuki;Hirao, Akiko;Shibata, Shigenobu
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