Effect of temporal distribution of macronutrient intake on metabolism

宏量营养素摄入时间分布对代谢的影响

• 批准号: 10657967
• 负责人: FRANK A SCHEER
• 金额: $ 80.23万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657967
• 关键词: Address; Area Under Curve; Behavioral; Beta Cell; Biological; Caloric Restriction; Carbohydrates; Cell physiology; Chronic; Circadian desynchrony; Data; Diet; Eating; Evidence based intervention; Fasting; Fatty acid glycerol esters; General Population; Glucose; Goals; Health; Indirect Calorimetry; Intake; Intervention; Knowledge; Life Style; Lipids; Macronutrients Nutrition; Measures; Metabolic; Metabolic Marker; Metabolism; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Oral; Phase; Play; Prevalence; Protocols documentation; Randomized; Randomized, Controlled Trials; Research; Research Design; Risk; Risk Factors; Role; Schedule; Sleep disturbances; Socioeconomic Status; Stress; System; Testing; Thermogenesis; Time; Triglycerides; Vulnerable Populations; Wakefulness; Work; balance testing; circadian; circadian pacemaker; design; diabetes risk; experimental study; glucose tolerance; impaired glucose tolerance; insight; insulin sensitivity; novel; novel strategies; oxidation; shift work; translational approach

Abstract The broad goal of this project is to determine whether shifting the temporal distribution of macronutrient intake impacts metabolic markers of health, which holds great translational value for vulnerable populations, including night shift workers. Night work is increasingly prevalent and a risk factor for type 2 diabetes (T2D). We and others have shown that circadian misalignment itself, i.e., the misalignment between the eating/fasting cycle and the central circadian timing system, leads to impaired glucose tolerance and decreased insulin sensitivity, even in chronic shift workers. Circadian misalignment is thus a likely mechanism contributing to the increased T2D risk in night workers. Because night work is not likely to go away anytime soon, countermeasures against these adverse metabolic effects are desperately needed. Our preliminary data from stringently-controlled circadian experiments suggests that glucose tolerance, beta-cell function, and diet-induced thermogenesis are increased in the circadian morning compared to the circadian evening, and that—in contrast—fat tolerance is increased in the circadian evening compared to the circadian morning. Based on these insights, we have developed a novel and translational approach that combines the concepts of the importance of WHAT we eat with the importance of WHEN we eat: scheduling high-carb intake for the circadian morning and high-fat intake for the circadian evening (C/F; expected to be favorable) as compared to vice versa (F/C, high-fat for circadian morning and high-carb for circadian evening), without changing 24-h caloric or macronutrient intake. Using two highly-controlled, within-subject, randomized, crossover protocols (one under circadian alignment, one under circadian misalignment), we will test the hypotheses that high-carb intake during the biological morning and high-fat intake during the biological evening (C-F) compared to vice versa (F-C) leads to: higher glucose tolerance (Aim 1); higher diet-induced thermogenesis (Aim 2); and higher fat tolerance (Exploratory Aim 3). We will test these aims in a robust and sophisticated study design: (1) without disturbing sleep during the day; (2) without requiring extended fasting during wakefulness at night; (3) without changing the caloric content per meal; and (4) without changing 24-h caloric or 24-h macronutrient intake. Knowledge on the health impacts of macronutrient intake timing is not only important for shift workers but also for the general population. Therefore, these questions will not only be addressed under circadian misalignment but also circadian alignment.

抽象的 该项目的广泛目标是确定是否改变了临时分布 大量营养素摄入影响健康的代谢标记，这具有巨大的翻译价值 对于包括夜班工人在内的脆弱人群。夜间工作越来越普遍， 2型糖尿病（T2D）的危险因素。我们和其他人表明昼夜节律错位 本身，即饮食/禁食周期与中央昼夜节律时机之间的错位 系统，导致葡萄糖耐量受损并降低胰岛素敏感性，即使在慢性中 轮班工人。因此，昼夜节律错位是可能导致增加的机制 夜间工人的T2D风险。因为夜间工作不太可能很快消失，所以 迫切需要针对这些不良代谢作用的对策。我们的 来自严格控制的昼夜节律实验的初步数据表明葡萄糖 在昼夜节律中，耐受性，β细胞功能和饮食诱导的热发生增加了 与昼夜的夜晚相比，早晨，相比之下 昼夜节律甚至与昼夜节日的早晨进行了比较。基于这些见解，我们有 开发了一种小说和翻译的方法，结合了重要性的概念 我们吃的东西的重要性：为昼夜节律安排高碳水化合物 比较昼夜节日的早晨和高脂摄入量（预计会有利） 反之亦然（f/c，昼夜节日早晨的高脂和昼夜夜晚的高碳水化合物），没有 更改24小时的热量或大量营养素摄入量。使用两个高度控制的主体内部 随机，交叉方案（一个在昼夜节律下，一个在昼夜节律下 未对准），我们将测试在生物学早晨和 与VICE（F-C）相比，在生物学之夜（C-F）的高脂摄入量导致：更高 葡萄糖耐受性（AIM 1）；饮食诱导的热发生较高（AIM 2）；和更高的脂肪耐受性 （探索目标3）。我们将以强大而复杂的研究设计测试这些目标：（1）没有 白天干扰睡眠； （2）不需要在晚上清醒期间延长禁食； （3）不需要每顿饭的热量含量； （4）不更改24小时卡路里或24小时 大量营养素摄入量。关于大量营养素摄入时机健康影响的知识不仅是 对于轮班工人而言，重要的是对普通人群。因此，这些问题不会 仅在昼夜节律未对准的情况下解决。