Froy O, Chapnik N, Miskin R
Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Neuroscience. 2008 Sep 9;155(4):1152-9. doi: 10.1016/j.neuroscience.2008.06.060. Epub 2008 Jul 4.
The circadian clock in the suprachiasmatic nuclei (SCN) responds to light and regulates peripheral circadian rhythms. Feeding regimens also reset the clock, so that time-restricted feeding (RF) dictates rhythms in peripheral tissues, whereas calorie restriction (CR) affects the SCN clock. To better understand the influence of RF vs. CR on circadian rhythms, we took advantage of the transgenic alphaMUPA mice that exhibit spontaneously reduced eating, and can serve as a model for CR under ad libitum feeding, and a model for temporal CR under RF compared with wild type (WT) mice. Our results show that RF advanced and generally increased the amplitude of clock gene expression in the liver under LD in both mouse types. However, under disruptive light conditions, RF resulted in a different clock gene phase in WT mice compared with alphaMUPA mice, suggesting a role for the reduced calories in resetting the SCN that led to the change of phase in alphaMUPA mice. Comparison of the RF regimen in the two lighting conditions in WT mice revealed that mPer1, mClock, and mBmal1 increased, whereas mPer2 decreased in amplitude under ultradian light in WT mice, suggesting a role for the SCN in determining clock gene expression in the periphery during RF. In summary, herein we reinforce a role for calorie restriction in resetting the SCN clock, and unravel a role for the SCN in determining peripheral rhythms under RF.
视交叉上核（SCN）中的生物钟对光作出反应并调节外周昼夜节律。进食方案也会重置生物钟，因此限时进食（RF）决定外周组织的节律，而热量限制（CR）则影响SCN生物钟。为了更好地理解RF与CR对昼夜节律的影响，我们利用了转基因αMUPA小鼠，这些小鼠表现出自发性进食减少，在自由进食条件下可作为CR的模型，与野生型（WT）小鼠相比，在RF条件下可作为限时CR的模型。我们的结果表明，在两种小鼠类型中，RF使肝脏中生物钟基因表达的相位提前并普遍增加了其振幅。然而，在紊乱光照条件下，与αMUPA小鼠相比，RF导致WT小鼠的生物钟基因相位不同，这表明减少的热量在重置SCN中发挥了作用，导致αMUPA小鼠相位改变。对WT小鼠两种光照条件下RF方案的比较显示，在超日光照下，WT小鼠的mPer1、mClock和mBmal1振幅增加，而mPer2振幅降低，这表明SCN在RF期间决定外周生物钟基因表达中发挥作用。总之，我们在此强化了热量限制在重置SCN生物钟中的作用，并揭示了SCN在RF条件下决定外周节律中的作用。
