Why we eat when: mechanisms underlying meal entrainment

为什么我们什么时候吃：膳食夹带的机制

• 批准号: 8201907
• 负责人: Megan Dailey
• 金额: $ 5.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-04 至 2013-07-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8201907
• 关键词: 5' -AMP-activated protein kinase; Animal Feed; Animals; Attenuated; Automobile Driving; Behavior; Behavioral; Biological; Cell Nucleus; Cells; Circadian Rhythms; Cues; Development; Digestion; Eating; Environment; Exhibits; Food; Food deprivation (experimental); Gene Expression; Gene Proteins; Genes; Human; Individual; Infusion procedures; Insulin; Intestines; Knockout Mice; Laboratory Rat; Lead; Learning; Light; Link; Liver; Metabolic; Metabolic Diseases; Metabolism; Modeling; Motivation; Neurobiology; Neurons; Nutrient; Obesity; Organ; Pancreas; Pathway interactions; Peripheral; Phase; Physiological; Physiology; Property; Psychological reinforcement; Rattus; Schedule; Signal Transduction; Sleep Wake Cycle; Stomach; Testing; Time; Tissues; base; body system; brain cell; circadian pacemaker; feeding; feeding schedule; ghrelin; glucagon-like peptide; mouse model; peptide hormone; release factor; response; sensor

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.

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。这些干扰可能是由于睡眠/觉醒周期的改变或计划进餐时间的改变而发生的。食物的生物学意义使得食物的时间供应对许多不同的行为或生理功能至关重要。人类和其他动物学会了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、午餐和晚餐上吃饭。人类和其他动物物种已经学会在一天中的特定时间期待食物，这表明餐前预期活动（食物预期活动；FAA）和肽/激素（胰岛素、胃饥饿素和胰高血糖素样肽-1）的增加。从多种生物钟基因敲除小鼠模型以及其他研究中可以看出，中枢和外周昼夜节律振荡器似乎对饭前行为和生理变化的驱动都很重要。然而，目前尚不清楚是什么用餐时间的线索真正设定了昼夜节律振荡器的节奏。尽管明暗周期对于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，也可以看到FAA（1,2）。这表明，除了光/暗循环之外，进餐的暗示也很重要。食物的内在特性（食物代谢产物或由于消化而释放的激素/肽）可能能够设置昼夜节律振荡器，从而驱动行为和生理的进一步变化。我建议在实验室大鼠中使用膳食干扰模型来了解食物如何与昼夜节律振荡器相互作用，昼夜节律振荡器负责代谢和肥胖发展中重要因子的表达/释放时间。这可以作为一个有用的模型，用于理解在昼夜节律改变的个体中代谢紊乱和肥胖倾向增加的潜在机制，以及更广泛地理解昼夜节律和喂养的神经生物学。