Time restricted feeding and metabolic rhythms in humans

人类的时间限制进食和代谢节律

基本信息

批准号：
10435774
负责人：
Corey Allan Rynders
金额：
$ 7.37万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-04-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10435774
关键词：
3-Dimensional Address Adipocytes Adipose tissue Affect Animals Biological Biological Assay Biology Biopsy Blood Blood specimen Body fat Caloric Restriction Calorimetry Catabolic Process Chronic Disease Circadian Rhythms Collaborations Colorado Consumption Crossover Design Data Development Diabetes Mellitus Diet Dietary Fats Dietary Practices Diurnal Rhythm Doctor of Philosophy Eating Eating Behavior Endocrine Energy Intake Ensure Fasting Fatty Acids Fatty acid glycerol esters Food Gene Expression Genes Glucose Goals Health High Fat Diet Homeostasis Hour Human Hypothalamic structure Inpatients Insulin Intake Intermittent fasting Intervention K-Series Research Career Programs Knowledge Life Life Style Light Link Lipids Liver Measures Medical Melatonin Metabolic Metabolic Diseases Metabolism Mus Muscle National Institute of Diabetes and Digestive and Kidney Diseases Obesity Observational Study Oral Participant Pattern Peripheral Phase Physical activity Physiology Plasma Play Posture Prevention Guidelines Protocols documentation Randomized Research Research Design Research Personnel Rodent Role Schedule Scientist Sleep Sleep Wake Cycle Societies System Testing Time Time-restricted feeding Tissues Tracer Training United States National Institutes of Health Universities Wakefulness Work awake base behavior influence career circadian circadian pacemaker circadian regulation diet-induced obesity dietary restriction feeding flexibility glucose metabolism glucose monitor glucose tolerance improved insulin sensitivity insulin signaling lifestyle factors lipid metabolism modifiable behavior multidisciplinary obesity risk obesity treatment overweight adults oxidation pre-clinical prevent programs response stable isotope translational scientist

项目摘要

Project Summary & Abstract The timing of energy intake relative to the light-dark and sleep-wake cycle plays an important role in the development of metabolic diseases. Consuming energy at an inappropriate time of day results in desynchrony of anabolic and catabolic processes that are regulated across the day by circadian clock systems. When mice are fed a high fat diet ad libitum, they eat throughout the day and night and become obese, but strikingly when the same diet is restricted to a short window at the appropriate circadian time (i.e., time-restricted feeding; TRF), they are protected against obesity. Little is known in humans regarding the influence of meal timing on whole body metabolism and the mechanisms involved. The overarching research goal of the present K01 Career Development Award is to leverage the pre-clinical evidence on the TRF paradigm to understand how meal timing affects fuel metabolism, metabolic flexibility, and the circadian landscape in humans. The proposed research plan serves as a vehicle to advance the applicant, Dr. Corey Rynders, PhD to independent investigator status over a period of five years of NIH-NIDDK K01 support. Dr. Wendy Kohrt at the University of Colorado – Anschutz Medical Campus and a multidisciplinary group of scientists with expertise in circadian physiology and metabolism (Drs. Wright, Bessesen, and Melanson) will oversee the training plan of Dr. Rynders and ensure his successful transition to an independent translational researcher. To achieve these aims, Dr. Rynders will need to gain new knowledge of circadian physiology, establish important collaborations in the circadian field, mature his expertise in metabolic research, and have protected time to acquire preliminary data to submit a competitive R01 application. The overall career goal is to develop an independent research program focused on how lifestyle factors impact the circadian regulation of metabolism in human participants. Study Design: The study will determine the effects of timed feeding on substrate metabolism, metabolic flexibility, and circadian rhythms measured in plasma and adipose tissue. Overweight adults (N=24) will undergo three 8-10d protocols (7d free-living; 1-3d inpatient) during which sleep timing remains consistent and energy-balanced meals are scheduled at- (a) 0.5h, 8h, and 15.5h after wake (prolonged feeding window); (b) 0.5h, 4h, and 8h after wake (early TRF); and (c) 8h, 12h, and 15.5h after wake (late TRF). Aim 1 will utilize stable isotope tracers and room calorimetry to test whether TRF increases dietary fat oxidation, 24h whole body fat oxidation, and the metabolic flexibility to fasting. Aim 2 will use continuous glucose monitoring and serial blood draws to determine whether TRF decreases 24h and postprandial glucose and insulin concentrations. Aim 3 will obtain fundamental data on whether meal timing and feeding duration results in phase shifts and/or amplitude changes in markers of the central clock (melatonin) and peripheral tissue clocks (e.g., endocrine rhythms measured in plasma and insulin signaling rhythms measured in adipose tissue). Relevance: Meal timing is a modifiable behavior and may be a strategy against obesity and metabolic disease.

项目摘要和摘要能量摄入相对于浅黑暗和睡眠效果周期的时机在代谢性疾病的发展。在不适当的时间消耗能量会导致脱节整天由昼夜节律系统调节的合成代谢过程。当老鼠时随意喂食高脂饮食，他们整夜都在吃饭，肥胖，但是当相同的饮食仅限于在适当的昼夜节律时（即，时间限制的喂食； trf），它们受到保护免受肥胖的保护。人类在餐时的影响中知之甚少全身代谢和所涉及的机制。当前K01的总体研究目标职业发展奖是要利用TRF范式上的临床前证据来了解如何进餐时机会影响燃料代谢，代谢柔韧性和人类的昼夜节律景观。拟议的研究计划是推动申请人Corey Rynders博士的工具在NIH-NIDDK K01支持的五年内，独立研究者的地位。温迪·科尔特（Wendy Kohrt）博士科罗拉多大学 - 安苏兹医学校园和一个多学科的科学家小组昼夜节律生理学和代谢方面的专业知识（赖特博士，贝森和梅兰森）将监督 Rynders博士的培训计划，并确保他成功地过渡到独立的翻译研究员。到实现这些目标，林德斯博士将需要获得昼夜节律生理学的新知识，建立重要的在昼夜节律领域的合作，使他在代谢研究方面的专业知识成熟，并保护了时间获取初步数据以提交竞争性R01申请。总体职业目标是发展独立研究计划的重点是生活方式因素如何影响新陈代谢的昼夜节律调节在人类参与者中。研究设计：研究将确定定时喂养对底物代谢，代谢的影响灵活性和在血浆和脂肪组织中测得的昼夜节律。超重成年人（n = 24）将接受三种8-10D方案（7D自由生活； 1-3d住院），在此期间睡眠时间保持一致，并且唤醒后（长时间的进食窗口）安排了能量平衡的餐点 - （a）0.5h，8h和15.5h；（b）唤醒后0.5h，4h和8h（早期TRF）；（c）唤醒后的8h，12h和15.5h（trf晚）。 AIM 1将使用稳定的同位素示踪剂和房间量热法以测试TRF是否增加饮食脂肪氧化，整个24小时体内脂肪氧化以及禁食的代谢灵活性。 AIM 2将使用连续的葡萄糖监测和抽血以确定TRF是否降低24h和餐后葡萄糖和胰岛素浓度。 AIM 3将获得有关进餐时间和喂养持续时间是否导致的基本数据相移和/或放大器的变化中央时钟（褪黑激素）和周围组织时钟的变化（例如，在脂肪组织中测得的血浆和胰岛素信号节律中测得的内分泌节奏）。相关性：进餐时机是一种可修改的行为，可能是反对肥胖和代谢的策略疾病。