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 该项目的总体目标是确定是否会改变 大量营养素的摄入会影响健康的代谢标志，具有巨大的转化价值 针对弱势群体，包括夜班工人。夜间工作越来越普遍 2 型糖尿病 (T2D) 的危险因素。我们和其他人已经证明昼夜节律失调 本身，即饮食/禁食周期与中央昼夜节律时间之间的不一致 系统，导致糖耐量受损和胰岛素敏感性降低，即使在慢性病中也是如此 轮班工人。因此，昼夜节律失调可能是导致增加的机制 夜间工作者的 T2D 风险。因为夜间工作不太可能很快消失， 迫切需要针对这些不利代谢影响的对策。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 昼夜节律中的耐受性、β细胞功能和饮食诱导的生热作用都会增加 与昼夜节律晚上相比，早上的脂肪耐受性会增加 昼夜节律晚上与昼夜节律早晨的比较。基于这些见解，我们有 开发了一种新颖的翻译方法，结合了重要性的概念 我们吃什么和什么时候吃的重要性：根据昼夜节律安排高碳水化合物摄入量 早晨和昼夜节律晚上的高脂肪摄入量（C/F；预计有利）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 小时热量或大量营养素的摄入量。使用两个高度控制的、主体内的、 随机、交叉方案（一种根据昼夜节律调整，一种根据昼夜节律 错位），我们将测试生物早晨期间高碳水化合物摄入量和 生物晚上 (C-F) 与反之亦然 (F-C) 相比，高脂肪摄入会导致： 葡萄糖耐量（目标 1）；更高的饮食诱导生热作用（目标 2）；和更高的脂肪耐受性 （探索性目标 3）。我们将通过稳健而复杂的研究设计来测试这些目标：（1）没有 白天扰乱睡眠； (2) 夜间清醒时无需长时间禁食； (3)不改变每餐的热量含量； (4) 不改变 24 小时热量或 24 小时 大量营养素的摄入。关于常量营养素摄入时间对健康影响的知识不仅是 对于轮班工人很重要，而且对于普通大众也很重要。因此，这些问题不会 只能在昼夜节律失调的情况下解决，但也可以在昼夜节律调整的情况下解决。