Why we eat when: mechanisms underlying meal entrainment

描述(申请人提供)：昼夜节律的紊乱，即身体的正常计时系统，可能会导致新陈代谢紊乱和肥胖。这些干扰可能是由于睡眠/醒来周期的改变或计划用餐时间的改变造成的。食物的生物学意义使得食物的时间供应对于许多不同的行为或生理功能至关重要。人类和其他动物物种学会将食物的可获得性与环境中的线索或食物固有的特性联系起来。我们把一天中的时间和吃饭联系在一起，所以我们通常在早餐、午餐和晚餐时吃饭。人类和其他动物物种已经学会了在一天中的特定时间期待食物，这一点从餐前预期活动(食物预期活动；FAA)和多肽/激素(胰岛素、Ghrelin和胰高血糖素样肽-1)的增加中可见一斑。许多不同生物钟基因敲除的小鼠模型以及其他研究表明，中枢和外周昼夜节律振荡器似乎都对推动用餐前的行为和生理变化起着重要作用。然而，目前还不清楚到底是什么用餐提示让昼夜节律振荡器有了节奏。虽然光/暗周期对设定许多昼夜节律很重要，但当动物处于恒定的光照或恒定的黑暗条件下时，就可以看到FAA(1，2)。这表明，除了光/暗周期外，食物夹带的信号也很重要。食物的内在属性(食物代谢物或消化后释放的激素/多肽)可能能够设置昼夜节律振荡器，以推动行为和生理的进一步变化。我建议使用实验室大鼠的食物夹带模型来了解食物如何与昼夜节律振荡器相互作用，后者负责新陈代谢和肥胖发展中重要因素的表达/释放时间。这可能是一个有用的模型，可以用来理解导致昼夜节律改变的个体代谢紊乱倾向增加和肥胖发展的潜在机制，以及更广泛地理解昼夜节律和摄食的神经生物学。

DESCRIPTION (provided by applicant): Disruptions in circadian rhythms, the normal timing system of the body, can lead to metabolic disorders and obesity. These disruptions can occur because of altered sleep/wake cycles or changes in scheduled mealtimes. The biological significance of food makes the temporal availability of meals critical for many different behavioral or physiological functions. Humans and other animal species learn to associate food availability with cues in the environment or properties intrinsic to the food. We associate times of the day with eating, so that we are normally eating meals at breakfast, lunch and dinner. Humans and other animal species have learned to expect food at certain times of the day as indicated by preprandial increases in both anticipatory activity (food anticipatory activity; FAA) and peptides/hormones (insulin, ghrelin and glucagon-like peptide-1). Both central and peripheral circadian oscillators appear to be important for driving the behavioral and physiological changes prior to mealtime as indicated from the many knockout mouse models of various circadian clock genes, as well as other studies. It is not clear, though, what mealtime cues actually set the circadian oscillators in rhythm. Although the light/dark cycle is important for setting many circadian rhythms, FAA can be seen when animals are under constant light or constant dark conditions (1, 2). This suggests that meal entrainment cues other than those for the light/dark cycle are important. Intrinsic properties of the food (food metabolites or hormones/peptides released as a result of digestion) may be able to set the circadian oscillators to drive further changes in behavior and physiology. I propose to use a model of meal entrainment in laboratory rats to understand how food interacts with circadian oscillators that are responsible for the timing of expression/release of factors important in metabolism and the development of obesity. This may serve as a useful model for understanding the underlying mechanisms responsible for the increased propensity of metabolic disorders and development of obesity in individuals with altered circadian cycles and for a more broadly based understanding of the neurobiology of circadian rhythms and feeding.