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 肥胖是一种持续的流行病，也是一个严重的公共卫生问题。预防性和治疗性干预措施 主要专注于饮食和体育锻炼，旨在了解机制并提高功效。尤其， 关于饮食中的大量营养素含量，特别是低脂肪与低脂肪与低脂肪的含量，存在长期的争论。 碳水化合物饮食可以帮助治疗体重。最近对昼夜节律参与的见解 能源平衡控制中的系统提供了一种新的视角来了解大量营养素之间的关系 摄入量和体重控制。我们和其他人表明，昼夜节律的破坏会导致不利 代谢作用，包括能量平衡控制机制的变化，可以增加肥胖风险。 的确，昼夜节律破坏是代谢疾病的公认关键危险因素，也是由 诺贝尔奖委员会授予三名昼夜节开拓者，授予2017年诺贝尔生理学或医学奖。 鉴于代谢与昼夜节律之间的亲密相互作用，已提出 饮食中的大量营养素含量可能会因昼夜节律的变化而部分影响全身生理 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 破坏了昼夜节律，包括节奏钝和昼夜节律时期（循环长度）。这些 发现与我们在人类的初步数据一致，在其中我们发现24小时的百分比较高 脂肪的摄入与（i）饥饿中钝化的内源性昼夜节律有关； （ii）较高的热量摄入量 生物之夜； （iii）内源性昼夜节律延长； （iv）延迟的内源性昼夜节律 阶段。综上所述，这些结果为高脂饮食引起的昼夜节律破坏提供了强有力的前提。 然而，尽管昼夜组织的重要性越来越认识到脂肪的影响 在昼夜节律系统上的摄入量，人类的实验数据非常有限，这已经测试了 高脂饮食在昼夜节律上或昼夜节律对代谢的控制。因此，在此提案中，我们将解决 通过检验以下假设来测试这些知识差距：与低脂饮食相比，高脂饮食导致 （AIM 1）中央时钟的内源性昼夜节律的钝化和延迟 外围钟； （目标2）在能量摄入中的每日和内源性昼夜节律中钝化和延迟 - 相关措施； （探索目的3）在每天和内源性昼夜节律中钝化和延迟 能源消耗相关的措施。这些目标将在主题内，随机，交叉中进行测试 在有两个方案的健康个体中设计。每个协议都有一个基于短期字段的 饮食干预（2周以避免重大体重变化），然后进行6天高度控制的内部 实验室参观。了解大量营养素摄入量与昼夜节律系统之间的联系将建立 基于证据的饮食干预的基础，将时间整合到预防和治疗肥胖症中 和代谢健康。