Metabolic Effects of Circadian-Based Dinner Time

基于昼夜节律的晚餐时间的代谢影响

• 批准号: 10667633
• 负责人: Daisy Duan
• 金额: $ 19.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667633
• 关键词: Acute; Adult; Award; Blood specimen; Circadian Rhythms; Circadian desynchrony; Dietary Fats; Eating; Enrollment; Fatty acid glycerol esters; Food; Foundations; Funding; Glucose; Goals; Grant; Hour; Human; Indirect Calorimetry; Individual; Insulin; Intervention; K-Series Research Career Programs; Late Effects; Lead; Leadership; Light; Measures; Melatonin; Mentors; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; Metabolism; Methods; Morbidity - disease rate; Obesity; Oral; Outcome; Output; Palmitates; Phase; Phenotype; Population; Prediabetes syndrome; Predisposition; Prevention; Randomized; Research; Research Methodology; Research Personnel; Sleep; System; Techniques; Time; Tracer; Training; Woman; Writing; actigraphy; adult obesity; analytical method; career; circadian; design; dietary; experience; feeding; hands-on learning; healthy weight; in vivo; insight; men; metabolic abnormality assessment; mortality; novel; obesity treatment; oxidation; precision medicine; prevent; programs; prospective; skills; symposium; Acute; Adult; Award; Blood specimen; Circadian Rhythms; Circadian desynchrony; Dietary Fats; Eating; Enrollment; Fatty acid glycerol esters; Food; Foundations; Funding; Glucose; Goals; Grant; Hour; Human; Indirect Calorimetry; Individual; Insulin; Intervention; K-Series Research Career Programs; Late Effects; Lead; Leadership; Light; Measures; Melatonin; Mentors; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; Metabolism; Methods; Morbidity - disease rate; Obesity; Oral; Outcome; Output; Palmitates; Phase; Phenotype; Population; Prediabetes syndrome; Predisposition; Prevention; Randomized; Research; Research Methodology; Research Personnel; Sleep; System; Techniques; Time; Tracer; Training; Woman; Writing; actigraphy; adult obesity; analytical method; career; circadian; design; dietary; experience; feeding; hands-on learning; healthy weight; in vivo; insight; men; metabolic abnormality assessment; mortality; novel; obesity treatment; oxidation; precision medicine; prevent; programs; prospective; skills; symposium

Obesity and its metabolic complications are leading causes of morbidity and mortality in the world. Evidence is mounting that inappropriate timing of food intake contributes to obesity. Late eating is associated with obesity and metabolic syndrome, suggesting that circadian misalignment may be the mechanism underlying the adverse metabolic consequences of late eating. We hypothesize that meal timing in relation to the endogenous circadian rhythm, rather than to clock hour, determines metabolic outcomes. In this study, we will use dim light melatonin onset (DLMO), the gold-standard for ascertaining central circadian output, to assess individual circadian rhythms. We will use DLMO to prospectively assign “early” (DLMO-3h) vs “late” (DLMO+1h) dinner while maintaining the same sleep times (DLMO+2h to +10h) to evaluate whether acute metabolic dysfunction can be reliably induced or prevented by setting dinner times around DLMO. We will use hourly blood sampling for detailed glucose and insulin profiles, oral [2H31] palmitate tracer to quantify dietary fat oxidation, and whole-room indirect calorimetry to measure total fat oxidation. We will enroll both normal-weight healthy adults (NWH) and adults with obesity and prediabetes (OPD), as the latter population is particularly vulnerable to metabolic diseases and could derive immediate benefit from our findings. The specific aims are to: 1) Quantify the impact of DLMO-based “early” vs. “late” dinner time on post-prandial and overnight glucose and insulin levels in NWH and OPD adults, 2) Measure the impact of DLMO-based “early” vs. “late” dinner time on (a) exogenous/dietary and (b) total fat oxidation in NWH and OPD adults, and 3) Examine the utility of circadian phase markers to predict susceptibility to late eating-induced metabolic dysfunction. For Aims 1 and 2, we will crossover-randomize 16 NWH adults (8 men, 8 women) and 16 OPD adults (8 men, 8 women) to the 2 dinner times with isocaloric feeding in a metabolic chamber. For Aim 3, we will leverage validated circadian metrics derived from actigraphy and ingestible thermosensors to predict effects of late dinner. Dr. Daisy Duan’s long-term career goal is to become an independent clinician investigator leveraging novel mechanistic insights that underly the intersection between the circadian system and metabolism to design and validate interventions for the prevention and treatment of obesity and its metabolic complications. She seeks a K23 mentored career development award to gain critical skills and experience in order to effectively lead an independently-funded research program. The goals during the award period include developing expertise in the design and implementation of in vivo metabolic studies and in the principles, practice, and analytical methods in sleep and circadian phenotyping techniques, through a combination of mentored research experience, focused coursework, hands-on learning in research methodology, participation in local and national conferences, grant writing, and leadership training and experience. The proposed study will lay the foundation for novel, circadian- based meal timing as a precision medicine approach to obesity and metabolic dysfunction.

肥胖及其代谢并发症是世界上发病和死亡率的主要原因。证据是 安装不适当的食物摄入时机会导致肥胖。晚餐与肥胖有关 和代谢综合征，这表明昼夜节律可能是不利的机制 晚期饮食的代谢后果。我们假设与内源性昼夜节律有关的饭菜时间 节奏而不是时钟小时决定了代谢结果。在这项研究中，我们将使用昏暗的光褪黑激素 发作（DLMO），是确定中央昼夜节律输出的金色标准，以评估单个昼夜节律。 我们将使用DLMO前瞻性地分配“早期”（DLMO-3H）与“ Late”（DLMO+1H）晚餐，同时保持 相同的睡眠时间（DLMO +2H至 +10H），以评估急性代谢功能障碍是否可靠 或通过在DLMO周围设置晚餐时间来阻止。我们将每小时抽水进行详细的葡萄糖和 胰岛素轮廓，口服[2H31]棕榈酸酯示踪剂以量化饮食脂肪氧化和全室间接量热法 测量总脂肪氧化。我们将注册正常体重健康的成年人（NWH）和肥胖成年人 和糖尿病前期（OPD），因为后一个人口特别容易患有代谢性疾病，并且可能导致 从我们的发现中受益。具体目的是：1）量化基于DLMO的“早期” VS的影响。 NWH和OPD成年人的餐后和过夜葡萄糖和胰岛素水平的“晚餐”时间，2） 基于DLMO的“早期”与“晚餐”时间对（a）外源/饮食和（b）总脂肪氧化的影响 NWH和OPD成年人，以及3）检查昼夜节相标预测晚期易感性的效用 饮食引起的代谢功能障碍。对于目标1和2，我们将跨界16个NWH成年人（8个人，8个人） 女性）和16名OPD成年人（8个男人，8个女性）到2个晚餐时间，与代谢中的等级喂养 腔室。对于AIM 3，我们将利用验证的昼夜节律指标 热能传感器可预测晚餐后期的影响。 Daisy Duan博士的长期职业目标是成为一个独立的临床研究者，利用小说 机械洞察力的见解是在设计和新陈代谢之间的交集下进行设计和 验证预防和治疗肥胖及其代谢并发症的干预措施。她寻求一个 K23指导职业发展奖，以获得关键技能和经验，以便有效地领导 独立资助的研究计划。奖励期内的目标包括在 体内代谢研究以及在原理，实践和分析方法中的设计和实施 睡眠和昼夜节律表型技术，通过修补研究经验的结合，集中精力 课程工作，研究方法中的动手学习，参加地方和民族会议，授予 写作，领导培训和经验。拟议的研究将为新颖的昼夜节律奠定基础 基于饮食时间作为肥胖和代谢功能障碍的精确药物方法。