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.

摘要 这个项目的主要目标是确定是否改变了时间分布， 宏量营养素摄入量影响健康的代谢指标，这具有很大的转化价值 包括夜班工人在内的弱势群体。夜间工作越来越普遍， 2型糖尿病（T2 D）的危险因素。我们和其他人已经证明，昼夜节律失调 本身，即，进食/禁食周期与中枢昼夜节律定时之间的不一致 系统，导致葡萄糖耐量受损和胰岛素敏感性降低，即使在慢性 轮班工人。因此，昼夜节律失调可能是一种机制，有助于增加 夜间工作者的T2 D风险因为夜班工作不太可能很快消失， 迫切需要对抗这些不利的代谢作用的对策。我们 严格控制的昼夜节律实验的初步数据表明，葡萄糖 耐受性、β细胞功能和饮食诱导的产热在昼夜节律中增加 与昼夜节律的晚上相比，早晨的脂肪耐受性增加， 昼夜节律的晚上和昼夜节律的早晨相比。基于这些见解，我们有 开发了一种新颖的翻译方法，结合了以下概念的重要性： 我们吃什么与我们吃的重要性：安排高碳水化合物摄入量的昼夜节律 上午和高脂肪摄入的昼夜节律晚上（C/F;预计是有利的）相比， 反之亦然（F/C，昼夜节律早上高脂肪，昼夜节律晚上高碳水化合物），没有 改变24小时热量或常量营养素摄入量。使用两个高度控制的，受试者内， 随机化、交叉方案（一个在昼夜节律调整下，一个在昼夜节律调整下， 失调），我们将测试的假设，高碳水化合物摄入量在生物上午， 在生物晚上（C-F）期间摄入高脂肪与反之亦然（F-C）相比，导致： 葡萄糖耐量（Aim 1）;较高的饮食诱导产热（Aim 2）;以及较高的脂肪耐量 （探索目标3）。我们将在一个强大而复杂的研究设计中测试这些目标：（1）没有 白天睡眠不好;（2）夜间清醒时不需要延长禁食; (3)不改变每餐的卡路里含量;（4）不改变24小时卡路里或24小时卡路里 大量营养素摄入量关于宏量营养素摄入时间对健康影响的知识不仅 这对轮班工人很重要，对一般人群也很重要。因此，这些问题不会 不仅在昼夜节律失调下解决，而且在昼夜节律对齐下解决。