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 该项目的主要目标是确定是否将时间分布 大量营养素的摄入影响健康的代谢标记物，这具有很大的翻译价值 针对弱势群体，包括夜班工人。夜班越来越普遍，而且 2型糖尿病(T2D)的危险因素。我们和其他人已经证明了昼夜节律失调 本身，即进食/禁食周期和中心昼夜节律之间的错位 系统，导致糖耐量受损和胰岛素敏感性降低，即使在慢性 倒班工人。因此，昼夜节律失调可能是导致 夜班工人的T2D风险。因为夜间工作不太可能在短期内消失， 迫切需要针对这些不利新陈代谢影响的对策。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 在昼夜节律中，耐受性、β细胞功能和饮食诱导的产热作用增加 早晨与昼夜相比，相比之下，脂肪耐受性在 昼夜与昼夜清晨的对比。基于这些洞察力，我们有 开发了一种新颖的翻译方法，该方法结合了 我们吃什么对我们吃什么很重要：为昼夜节律安排高碳水化合物的摄入量 比较早晨和夜间的高脂肪摄入量(C/F；预计是有利的) 反之亦然(F/C，昼夜高脂肪，夜间高碳水化合物)，不含 改变24小时卡路里或常量营养素摄入量。使用两个高度受控的受试者内部， 随机、交叉方案(一个在昼夜节律排列下，一个在昼夜节律排列下 错位)，我们将检验这样的假设：在生物清晨和 在生物夜晚摄入高脂肪(C-F)与反之亦然(F-C)相比，会导致：更高 糖耐量(目标1)；更高的饮食诱导产热(目标2)；以及更高的脂肪耐量 (探索性目标3)。我们将在稳健和复杂的研究设计中测试这些目标：(1)没有 白天扰乱睡眠；(2)夜间清醒时不需要延长禁食时间； (3)不改变每餐的卡路里含量；(4)不改变24小时或24小时的热量 常量营养素摄入量。对大量营养素摄入时机对健康影响的了解不仅仅是 这对倒班工人很重要，对普通民众也很重要。因此，这些问题不会 不仅在昼夜节律错位的情况下解决，而且也在昼夜节律对齐的情况下解决。