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.

抽象的 肥胖是一种持续存在的流行病，也是一个严重的公共卫生问题。预防和治疗干预措施 主要关注饮食和身体活动，旨在了解机制并提高疗效。尤其， 关于饮食中的宏量营养素含量，特别是低脂肪还是低脂肪，一直存在长期争论。 碳水化合物饮食有助于控制体重。关于昼夜节律参与的最新见解 能量平衡控制系统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。我们和其他人已经证明，昼夜节律系统的破坏会导致不利的结果。 代谢影响，包括可能增加肥胖风险的能量平衡控制机制的变化。 事实上，昼夜节律紊乱是公认的代谢紊乱的关键危险因素，这一点也得到了医学界的认可。 诺贝尔奖委员会将 2017 年诺贝尔生理学或医学奖授予三位昼夜节律先驱。 鉴于新陈代谢和生物钟之间密切的相互作用，有人提出 膳食大量营养素含量可能部分通过昼夜节律的变化影响全身生理机能 组织。一致地，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，包括节律迟钝和昼夜节律周期（周期长度）延长。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 脂肪摄入量与以下因素有关：（i）饥饿时内源性昼夜节律减弱； (ii) 较高的热量摄入 生物之夜； (iii) 内源性昼夜节律周期延长； (iv) 延迟的内源性昼夜节律 阶段。总而言之，这些结果为高脂肪饮食引起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组织的重要性和脂肪的影响 摄入量对昼夜节律系统的影响，在人类中测试其影响的实验数据非常有限 高脂肪饮食对生物钟或新陈代谢的昼夜节律进行控制。因此，在本提案中，我们将解决 通过测试以下假设来弥补这些知识差距：与低脂肪饮食相比，高脂肪饮食会导致 （目标 1）减弱和延迟中央生物钟的内源性昼夜节律以及与生物钟相关的措施 外设时钟； （目标 2）减弱和延迟每日和内源性昼夜节律的能量摄入 - 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、交叉中进行测试 在接受两种方案的健康个体中进行设计。两种协议都有一个短期的基于现场的 饮食干预（两周以避免体重大幅变化），然后是为期 6 天的高度控制的饮食干预 实验室参观。了解大量营养素摄入与昼夜节律系统之间的联系将为 为循证饮食干预奠定基础，整合预防和治疗肥胖的时机 和代谢健康。