Why we eat when: mechanisms underlying meal entrainment

描述（由申请人提供）：昼夜节律（身体的正常计时系统）的中断可导致代谢紊乱和肥胖。这些中断可能是由于睡眠/觉醒周期的改变或预定用餐时间的变化而发生的。食物的生物学意义使得膳食的时间可用性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了将食物的可用性与环境中的线索或食物固有的特性联系起来。我们将一天中的时间与吃联系起来，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的某些时间期待食物，如通过餐前预期活动（食物预期活动; FAA）和肽/激素（胰岛素、生长激素释放肽和胰高血糖素样肽-1）的增加所指示的。中枢和外周昼夜节律振荡器似乎对驱动进餐前的行为和生理变化都很重要，这一点从多种昼夜节律钟基因的许多敲除小鼠模型以及其他研究中得到了证实。然而，究竟是什么样的进餐时间信号使昼夜节律振荡器处于节律中，目前还不清楚。虽然光/暗周期对于设定许多昼夜节律很重要，但当动物处于恒定光照或恒定黑暗条件下时，可以看到FAA（1，2）。这表明，膳食夹带线索以外的光/暗周期是重要的。食物的内在特性（食物代谢物或消化后释放的激素/肽）可能能够设置昼夜节律振荡器，以驱动行为和生理的进一步变化。我建议使用一个模型，在实验室大鼠的膳食夹带，以了解食物如何与昼夜节律振荡器，负责表达/释放的重要因素的代谢和肥胖的发展的时间相互作用。这可能是一个有用的模型，了解的潜在机制，负责代谢紊乱的倾向增加和肥胖的发展，在个人改变昼夜节律周期和更广泛的基础上了解昼夜节律和喂养的神经生物学。 公共卫生相关性：将器官特异性或细胞核特异性振荡器的单独贡献分开，可能有助于识别代谢异常、肥胖和进食动机增加的途径中的重要成分。

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. PUBLIC HEALTH RELEVANCE: Teasing apart the separate contributions of organ-specific or nuclei-specific oscillators may help in identifying important components in a pathway responsible for metabolic abnormalities, obesity and the increased motivation to eat.