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Uncovering the Impact of Diet on the Human Circadian Timing System

揭示饮食对人类昼夜节律系统的影响

基本信息

批准号：
10475344
负责人：
Andrew William McHill
金额：
$ 56.97万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10475344
关键词：
Affect American Animal Model Area Behavior Biological Biological Clocks Biological Process Biomedical Research Blood Pressure Blood Vessels Calories Cardiovascular Diseases Chronic Disease Circadian Rhythms Circadian desynchrony Consumption Data Diabetes Mellitus Diet Dietary Practices Eating Economically Deprived Population Energy Metabolism Environment Exposure to Fat-Restricted Diet Fatty acid glycerol esters Foundations Future Goals Health High Fat Diet Hour Human Impaired cognition Impaired health Impairment Income Individual Inpatients Jet Lag Syndrome Laboratories Life Expectancy Light Melatonin Metabolic syndrome Mus Myocardial Infarction Obesity Outcome Outpatients Personal Satisfaction Persons Phase Physiological Physiology Process Public Health Randomized Risk Rodent Rodent Model Savings Schools Sleep Sleep disturbances Societies Speed Stimulus System Teenagers Testing Time Traffic accidents Translating Travel Wakefulness Woman Work cardiometabolism circadian circadian pacemaker cognitive function cognitive performance design dietary disorder risk experience geographic difference glucose tolerance granulysin improved insight insulin sensitivity men novel obese patients programs response sleep onset social sudden cardiac death sustained attention theories young adult

项目摘要

Summary/Abstract Synchronization of biological processes and behaviors with the 24-hour light-dark cycle is fundamental to optimal physiology, cognitive function, and health. Because humans have, on average, a longer than 24-hour internal clock, most people must perform this synchronization process on a daily basis. An inability to adequately entrain internal circadian rhythms to the external environment, even a small misalignment, can have severe consequences including poor cardiometabolic outcomes (i.e., cardiovascular disease, diabetes, obesity), impaired sleep, reduced cognitive performance, and even economic disadvantage. Entrainment is believed to be entirely orchestrated by exposure to morning light, as it has been assumed that non-photic exogenous stimuli have little influence on circadian entrainment in humans. However, emerging evidence from animal models indicates that circadian entrainment to light could be hampered by dietary composition. Specifically, mice fed a high-fat diet have a 20% slower rate of entrainment to light and a longer circadian period. If these findings hold true in humans, this would challenge current theory within the field of human circadian physiology and would have vast public health implications because so many Americans consume high-fat diets. Thus, quantifying the interaction between typical dietary choices and circadian entrainment has great importance. The goal of this project is to determine if these diet-related circadian effects in rodents translate to humans. Our specific aims are to establish the impact of a high-fat diet on the: 1) rate of entrainment of the circadian system to light; 2) circadian period and the resultant circadian timing of daily behaviors i.e., phase angle of entrainment (time difference between melatonin and sleep onsets); and 3) how the combination of eating a high-fat diet and circadian phase (i.e., circadian alignment vs misalignment) impacts cardiometabolic health and cognitive function. To accomplish our aims, we have designed a randomized cross-over mechanistic study in controlled laboratory settings. We hypothesize that when individuals that habitually eat a low-fat diet are provided an isocaloric high-fat diet (versus when provided an isocaloric low-fat diet), they will take longer to entrain to a shift in the light-dark cycle, have a narrower phase angle of entrainment, and have increased circadian misalignment and associated impairments in cardiometabolic health and cognitive function. These data will provide a fundamental understanding of how common dietary patterns alter the way humans synchronize to the environment. Importantly, these data would have far-reaching implications for the large portions of society that endure: 1) travel across multiple time zones (jet-lag); 2) a need to readjust sleep/wake timing on workdays (social jet-lag); and 3) work and school start times that are too early for the natural internal clock timing of most young adults and teens. This study is important because of the ubiquity of the need for circadian adjustments and the fact that even slight effects of diet on circadian entrainment can have large effects on human health and cognitive function.

摘要/摘要生物过程和行为与24小时光暗周期的同步是优化的基础生理学、认知功能和健康。因为人类平均有超过24小时的时钟，大多数人必须每天执行此同步过程。无法充分地内部昼夜节律与外部环境的失调，即使是很小的失调，后果包括不良的心脏代谢结果（即，心血管疾病、糖尿病、肥胖症），睡眠受损，认知能力下降，甚至经济上的劣势。夹带被认为是完全由暴露在晨光中精心策划，因为它已被假定为非光的外源性刺激，对人类的昼夜节律影响不大。然而，来自动物模型的新证据表明，昼夜夹带光可能会受到饮食组成的阻碍。具体地说，高脂肪饮食具有20%慢的对光的夹带速率和更长的昼夜节律周期。如果这些发现成立在人类中，这将挑战人类昼夜生理学领域的当前理论，对公众健康有着巨大的影响，因为很多美国人都在吃高脂肪的食物。因此，量化典型的饮食选择和昼夜变化之间的相互作用非常重要。这个目标该项目的目的是确定啮齿动物中与饮食有关的昼夜节律效应是否会转化为人类。我们的具体目标建立高脂饮食对以下方面的影响：1）昼夜节律系统对光线的夹带率; 2）昼夜节律周期和由此产生的日常行为的昼夜节律定时，即，卷吸相位角（时间褪黑激素和睡眠发作之间的差异）;以及3）吃高脂肪饮食和昼夜节律相位（即，昼夜节律调整与失调）影响心脏代谢健康和认知能力功能为了实现我们的目标，我们设计了一项随机交叉机制研究，实验室设置。我们假设，当习惯吃低脂饮食的人获得等热量的高脂肪饮食（与等热量的低脂肪饮食相比），他们将需要更长的时间来转变在明-暗周期中，具有较窄的夹带相位角，并且具有增加的昼夜失调以及心脏代谢健康和认知功能的相关损害。这些数据将提供基本了解常见的饮食模式如何改变人类同步到环境重要的是，这些数据将对社会的大部分人产生深远的影响，忍受：1）跨多个时区旅行（时差）; 2）需要在工作日重新调整睡眠/唤醒时间（社交）时差）;以及3）工作和学校开始时间对于大多数年轻人的自然内部时钟时间来说太早成人和青少年。这项研究很重要，因为昼夜节律调整的需要无处不在，事实上，即使饮食对昼夜节律的轻微影响也会对人类健康和认知能力产生重大影响。功能