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小时浅黑暗周期的同步是最佳的生理学，认知功能和健康。因为人类平均内部超过24小时时钟，大多数人必须每天执行此同步过程。无法充分夹带内部昼夜节律对外部环境的节奏，即使是微小的未对准，也可能有严重的后果包括较差的心脏代谢结果（即心血管疾病，糖尿病，肥胖），睡眠障碍，认知表现降低甚至经济劣势。据信夹带通过暴露于早晨的光线来精心策划，因为已经假定非晶状体外源对人类的昼夜节律的影响很小。但是，来自动物模型的新兴证据表明昼夜节律夹带可能会受到饮食成分的阻碍。具体来说，喂养的小鼠高脂饮食的夹带速度慢20％，昼夜节律较长。如果这些发现成立在人类中，这将挑战人类生理学领域的当前理论，并将具有巨大的公共卫生影响，因为如此多的美国人消耗高脂饮食。因此，量化典型的饮食选择与昼夜节律夹带之间的相互作用非常重要。目标的目标项目是确定这些与饮食相关的昼夜节律是否在啮齿动物中转化为人类。我们的具体目标是要建立高脂饮食对以下方面的影响：1）昼夜节律系统夹带的速度； 2）昼夜节律时期和每日行为的昼夜节律时间，即夹带的相位角度（时间褪黑激素和睡眠进对之间的差异）； 3）如何吃高脂饮食和昼夜节律阶段（即昼夜节律与未对准）影响心脏代谢健康和认知功能。为了实现我们的目标，我们在受控中设计了一项随机的交叉机械研究实验室环境。我们假设，当提供习惯性吃低脂饮食的人时等量水平的高脂饮食（与提供等量平衡的低脂饮食相比），它们需要更长的时间才能纳入转变在浅黑暗周期中，夹带的相位角度较窄，并增加了昼夜节律的未对准以及心脏代谢健康和认知功能的相关障碍。这些数据将提供对共同饮食模式如何改变人类同步的方式的基本理解环境。重要的是，这些数据将对社会的大部分地区具有深远的影响忍耐：1）跨多个时区（喷射滞后）； 2）需要在工作日重新调整睡眠/唤醒时间（社交喷气滞后）; 3）对于大多数年轻的天然内部时钟时间来说，工作和学校的起点还为时过早成人和青少年。这项研究很重要，因为需要调整昼夜节律和饮食对昼夜节律夹带的轻微影响也会对人类健康和认知产生巨大影响功能。