Metabolic Effects of Circadian-Based Dinner Time

基于昼夜节律的晚餐时间的代谢影响

基本信息

批准号：
10506606
负责人：
Daisy Duan
金额：
$ 20.02万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
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/10506606
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 Gold 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 base 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

项目摘要

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.

有证据表明，肥胖及其代谢并发症是世界范围内发病和死亡的主要原因。越来越多的人认为，进食时间不当会导致肥胖。和代谢综合征，表明昼夜节律失调可能是不良后果的机制我们渴望与内源性昼夜节律相关的进餐时间。节奏，而不是时钟时间，决定了代谢结果。在这项研究中，我们将使用弱光褪黑激素。发病（DLMO），确定中央昼夜节律输出的黄金标准，以评估个人昼夜节律。我们将使用 DLMO 前瞻性地分配“早”(DLMO-3h) 与“晚”(DLMO+1h) 晚餐，同时保持相同的睡眠时间（DLMO+2h至+10h）来评估是否可以可靠地诱导急性代谢功能障碍或通过在 DLMO 附近设置晚餐时间来预防。我们将每小时进行一次血液采样以获取详细的血糖和血糖。胰岛素曲线、口服 [2H31] 棕榈酸酯示踪剂以量化膳食脂肪氧化，以及全室间接量热法为了测量总脂肪氧化，我们将招募正常体重的健康成年人 (NWH) 和肥胖成年人。和糖尿病前期 (OPD)，因为后者特别容易罹患代谢性疾病，并可能导致我们的研究结果可立即带来好处，具体目标是：1）量化基于 DLMO 的“早期”与“后期”的影响。 “晚”晚餐时间对 NWH 和 OPD 成人餐后和夜间血糖和胰岛素水平的影响，2) 测量基于 DLMO 的“早”与“晚”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) 检查昼夜节律阶段标记的效用，以预测对晚期的易感性对于目标 1 和 2，我们将对 16 名 NWH 成年人（8 名男性，8 名）进行交叉随机分组。女性）和 16 名 OPD 成人（8 名男性，8 名女性）在代谢组中进行 2 次晚餐等热量喂养对于目标 3，我们将利用源自活动记录和摄入的经过验证的昼夜节律指标。热传感器来预测晚餐的影响。 Daisy Duan 博士的长期职业目标是成为一名独立的临床研究者，利用新颖的方法昼夜节律系统和新陈代谢之间交叉点的机制见解，以设计和验证预防和治疗肥胖及其代谢并发症的干预措施。 K23 指导职业发展奖以获得关键技能和经验，以便有效领导独立资助的研究计划的目标包括发展专业知识。体内代谢研究的设计和实施以及体内代谢研究的原理、实践和分析方法睡眠和昼夜节律表型技术，通过结合指导研究经验，重点关注课程作业、研究方法的实践学习、参加地方和国家会议、资助写作、领导力培训和经验。拟议的研究将为小说、昼夜节律奠定基础。基于进餐时间作为治疗肥胖和代谢功能障碍的精准医学方法。