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

• 批准号: 10443069
• 负责人: Andrew William McHill
• 金额: $ 64.67万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443069
• 关键词: Adolescent; American; Animal Model; Animals; Area; Attention; Behavior; Biological; Biological Clocks; Biological Process; Biomedical Research; Blood Vessels; Calories; Cardiovascular Diseases; Chronic Disease; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Consumption; Data; Diabetes Mellitus; Diet; Dietary Practices; Eating; Energy Metabolism; Environment; Exposure to; Fat-Restricted Diet; Fatty acid glycerol esters; Foundations; Future; Goals; Health; High Fat Diet; Hour; Human; Impaired cognition; Impairment; Individual; Inpatients; Jet Lag Syndrome; Laboratories; Learning; Length; Life Expectancy; Light; Melatonin; Metabolic syndrome; Mus; Myocardial Infarction; Obesity; Outcome; Outpatients; Performance; Personal Satisfaction; Persons; Phase; Physiological; Physiology; Process; Public Health; Randomized; Rodent; Rodent Model; Savings; Schedule; Schools; Sleep; Sleep disturbances; Societies; Speed; Stimulus; Students; System; Teenagers; Testing; Time; Traffic accidents; Translating; Travel; Woman; Work; cardiometabolism; circadian; circadian pacemaker; cognitive function; design; dietary; disorder risk; experience; geographic difference; granulysin; improved; insight; insulin sensitivity; men; novel; obese patients; programs; response; sleep onset; social; sudden cardiac death; theories; western diet; young adult

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) and impaired sleep, cognitive function, and learning. 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 as 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) and the rate of re-entrainment impacts cardiometabolic health, cognitive function, and learning. 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, cognitive function, and learning. These data will provide a fundamental understanding of how common dietary patterns alter the way humans synchronize to the environment. Importantly, these data will 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 circadian clock 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 health, cognitive function, and learning.

摘要/摘要 生物过程和行为与24小时浅黑暗周期的同步至关重要 最佳生理，认知功能和健康。因为人类平均具有超过24小时的时间 内部时钟，大多数人必须每天执行此同步过程。无法 充分夹带外部环境的昼夜节律内部节奏，即使是小小的错位也可以 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， 肥胖症）和睡眠受损，认知功能和学习。人们认为夹带完全是 通过暴露于晨光来精心策划，因为已经假定非细胞外源刺激具有 对人类昼夜节律的影响很小。但是，来自动物模型的新兴证据表明 饮食成分可能会阻碍昼夜节律夹带。具体而言，小鼠喂了高脂 饮食的夹带速度慢20％，昼夜节律较长。如果这些发现成真 人类，这将挑战人类生理学领域的当前理论，并将 由于许多美国人消耗高脂饮食，巨大的公共卫生影响。因此，量化相互作用 在典型的饮食选择和昼夜节律夹带之间非常重要。这个项目的目标是 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。我们的具体目的是 建立高脂饮食对以下方面的影响：1）昼夜节律夹带的速度； 2）昼夜节律 周期和由此产生的日常行为的昼夜节律时间，即夹带的相位角度（时差） 在褪黑激素和睡眠攻击之间）； 3）如何饮食高脂饮食和昼夜节律的结合 （即昼夜节律与未对准的昼夜节律）和重新融合的速率会影响心脏代谢的健康， 认知功能和学习。为了实现我们的目标，我们设计了一个随机交叉 在受控实验室环境中的机械研究。我们假设，当习惯吃的人 提供低脂饮食是一种等量水平的高脂饮食（与提供等效低脂饮食相比），他们将 需要更长的时间来纳入光黑暗周期，具有较窄的夹带角度，并具有 心脏代谢健康，认知功能中的昼夜节律未对准和相关损害增加， 和学习。这些数据将对共同饮食模式如何改变的基本了解 人类与环境同步。重要的是，这些数据将对 忍受的大部分社会：1）跨越多个时区（喷射滞后）； 2）需要重新调整 在工作日的睡眠/唤醒时间（社交喷射滞后）； 3）工作和上学的开始时间为时过早 大多数年轻人和青少年的昼夜节律。这项研究很重要，因为需要 昼夜节律的调整以及饮食对昼夜节律夹带的轻微影响也可能具有较大的事实 对健康，认知功能和学习的影响。