Effect of high fat diet on the circadian system and on circadian rhythms in energy intake and expenditure

高脂肪饮食对昼夜节律系统以及能量摄入和支出的昼夜节律的影响

• 批准号: 10632907
• 负责人: FRANK A SCHEER
• 金额: $ 80.51万
• 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: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10632907
• 关键词: Animal Experiments; Award; Behavior; Biological; Body Weight Changes; Body Weight decreased; Carbohydrates; Chronic; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Consensus; Crossover Design; Data; Desire for food; Diet; Dietary Fats; Dietary Intervention; Dietary intake; Disease; Eating; Energy Intake; Energy Metabolism; Epidemic; Epidemiology; Exposure to; Fat-Restricted Diet; Fatty acid glycerol esters; Feeding behaviors; Goals; Health; High Fat Diet; Hormones; Human; Hunger; Individual; Intake; Jet Lag Syndrome; Knowledge; Laboratories; Length; Life Style; Life Style Modification; Light; Link; Macronutrients Nutrition; Measures; Medicine; Metabolic; Metabolic Diseases; Metabolism; Motor Activity; Nobel Prize; Obesity; Obesity Epidemic; Organ; Pathogenicity; Peripheral; Phase; Physical activity; Physiology; Play; Prevalence; Prevention; Protocols documentation; Public Health; Randomized; Regulation; Research; Risk; Risk Factors; Role; Sleep; System; Testing; Therapeutic; Therapeutic Intervention; Tissues; Visit; Weight maintenance regimen; Work; circadian; circadian pacemaker; combat; design; dietary; energy balance; evidence base; human data; improved; insight; ketogentic; novel; obesity risk; obesity treatment; preventive intervention; shift work; social

Abstract Obesity is an ongoing epidemic and a serious public health problem. Preventative and therapeutic interventions have mostly focused on diet and physical activity, aimed to understand mechanism and improve efficacy. Notably, there has been a long-term debate over whether macronutrient content in the diet, specifically a low fat vs. low carbohydrate diet can help in management of body mass. Recent insights into the involvement of the circadian system in energy balance control offer a new perspective to understand the relationship between macronutrient intake and weight control. We and others have shown that disruption of the circadian system leads to adverse metabolic effects, including changes in energy balance control mechanisms that can increase the risk for obesity. Indeed, circadian disruption is a recognized critical risk factor for metabolic disorders, as also recognized by the Nobel Prize Committee who awarded the 2017 Nobel Prize in Physiology or Medicine to three circadian pioneers. Given the intimate reciprocal interactions between metabolism and the circadian clock, it has been proposed that dietary macronutrient content may impact whole-body physiology in part through changes in the circadian organization. Consistently, breakthrough animal experimental work has shown that high fat diet leads to disrupted circadian rhythms, including blunted rhythms and lengthened circadian period (cycle length). These findings are consistent with our Preliminary Data in humans, in which we found that higher percentage of 24-h fat intake is associated with (i) a blunted endogenous circadian rhythm in hunger; (ii) a higher caloric intake in the biological evening; (iii) lengthened endogenous circadian period; and (iv) a delayed endogenous circadian phase. Taken together, these results provided strong premise for high fat diet-induced circadian disruption. However, despite the growing realization of the importance of circadian organization and the influence of fat intake on the circadian system, there is very limited experimental data in humans that has tested the effect of high fat diet on the circadian clock or circadian control of metabolism. Therefore, in this proposal, we will address these knowledge gaps by testing the following hypotheses: high fat diet, as compared to low fat diet results in (Aim 1) blunting and delaying of endogenous circadian rhythms of the central clock and measures related to the peripheral clocks; (Aim 2) blunting and delaying in daily and endogenous circadian rhythms in energy intake- related measures; (Exploratory Aim 3) blunting and delaying in daily and endogenous circadian rhythms in energy expenditure-related measures. These aims will be tested in a within-subject, randomized, crossover design in healthy individuals undergoing two protocols. Each of both protocols has a short-term field-based dietary intervention (2 weeks to avoid substantial weight change) followed by a 6-day highly controlled in- laboratory visit. Understand the link between macronutrient intake and the circadian system will lay the groundwork for evidence-based dietary intervention integrating timing in the prevention and treatment of obesity and metabolic health.

摘要 肥胖症是一种流行病，也是一个严重的公共卫生问题。预防和治疗干预 主要集中在饮食和体力活动，旨在了解机制和提高疗效。值得注意的是， 长期以来，人们一直在争论饮食中的常量营养素含量，特别是低脂还是低脂。 碳水化合物饮食可以帮助管理体重。最近的见解参与昼夜节律 系统能量平衡控制为理解大量营养素之间的关系提供了新的视角 摄入量和体重控制。我们和其他人已经表明，昼夜节律系统的破坏会导致不利的 代谢影响，包括能量平衡控制机制的变化，可能会增加肥胖的风险。 事实上，昼夜节律紊乱是公认的代谢紊乱的关键风险因素，也被《世界卫生组织》所认识到。 诺贝尔奖委员会将2017年诺贝尔生理学或医学奖授予了三位昼夜节律先驱。 鉴于新陈代谢和生物钟之间的密切相互作用， 饮食中的大量营养素含量可能会通过昼夜节律的变化影响全身生理学 organization.然而，突破性的动物实验工作表明，高脂肪饮食会导致 昼夜节律紊乱，包括节律变钝和昼夜周期延长（周期长度）。这些 研究结果与我们在人类中的初步数据一致，我们发现24小时的百分比较高， 脂肪摄入与（i）饥饿时的内源性昼夜节律减弱;（ii）饥饿时的高热量摄入有关。 生物学的夜晚;（iii）延长的内源性昼夜节律周期;和（iv）延迟的内源性昼夜节律 相位综上所述，这些结果为高脂饮食诱导的昼夜节律紊乱提供了强有力的前提。 然而，尽管人们越来越认识到昼夜节律的重要性和脂肪的影响， 摄入量对昼夜节律系统的影响，在人类中测试 高脂肪饮食对生物钟或新陈代谢的昼夜控制。因此，在本提案中，我们将解决 这些知识差距通过测试以下假设：高脂肪饮食，与低脂肪饮食相比， (Aim 1）中枢时钟的内源性昼夜节律的钝化和延迟，以及与中枢时钟相关的措施。 外周生物钟;（目标2）能量摄入的每日和内源性昼夜节律变钝和延迟- 相关措施;（探索性目标3）钝化和延迟日常和内源性昼夜节律， 能源支出相关措施。这些目标将在受试者内、随机、交叉中进行检验。 设计在健康个体经历两个协议。这两种协议都有一个短期的基于实地的 饮食干预（2周，以避免实质性的体重变化），然后是6天的高度控制， 实验室访问了解大量营养素摄入和昼夜节律系统之间的联系将奠定 循证饮食干预结合肥胖防治时机的基础 和代谢健康。