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小时光-暗周期的同步是 最佳生理机能、认知功能和健康。因为人类平均有超过24小时的 内部时钟，大多数人必须每天执行此同步过程。无力 充分地将内部昼夜节律带入外部环境，即使是很小的失调， 具有严重的后果包括不良的心脏代谢结果（即，心血管疾病，糖尿病， 肥胖）和睡眠、认知功能和学习受损。夹带被认为是完全 精心策划的暴露在早晨的光，因为它已被假定，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， 饮食结构可能会阻碍昼夜节律对光线的影响。具体地说，小鼠喂食高脂肪 饮食具有20%的慢夹带率到光和更长的昼夜节律周期。如果这些发现在 这将挑战人类昼夜生理学领域的现有理论， 巨大的公共健康影响，因为如此多的美国人消费高脂肪饮食。因此，量化相互作用 典型的饮食选择和昼夜变化之间的联系非常重要。该项目的目标是 确定啮齿类动物中这些与饮食有关的昼夜节律效应是否会转化为人类。我们的具体目标是 确定高脂肪饮食对以下方面的影响：1）昼夜节律系统对光线的引导率; 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，夹带相位角（时间差 褪黑激素和睡眠发作之间的关系）;以及3）高脂肪饮食和昼夜节律相结合 (i.e.,昼夜节律对准对未对准）和再夹带的速率影响心脏代谢健康， 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进行的机制研究。我们假设，当一个人习惯性地吃 低脂肪饮食提供等热量的高脂肪饮食（相对于当提供等热量的低脂肪饮食），他们将 需要更长的时间来夹带到亮-暗循环中的转变，具有更窄的夹带相位角，并且具有 增加的昼夜节律失调和相关的心脏代谢健康，认知功能， 和学习这些数据将提供一个基本的了解如何共同的饮食模式改变 人类与环境同步的方式。重要的是，这些数据将对未来产生深远的影响。 大部分人忍受着：1）穿越多个时区（时差）; 2）需要重新调整 工作日的睡眠/醒来时间（社会时差）;以及3）工作和学校的开始时间对于 大多数年轻人和青少年的生物钟。这项研究很重要，因为人们普遍需要 昼夜节律的调整和事实，即使是轻微的影响，饮食对昼夜节律的夹带可以有很大的 对健康、认知功能和学习的影响