Uncovering Circadian Mechanisms of Poor Cardiometabolic Health

揭示心脏代谢健康不良的昼夜节律机制

基本信息

批准号：
10383773
负责人：
Andrew William McHill
金额：
$ 12.63万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383773
关键词：
Acute Adult American Area Automobile Driving Behavior Body Weight Body Weights and Measures Body fat Businesses Calories Car Phone Carbohydrates Cardiometabolic Disease Chronic Clinical Consumption Data Diet Diet Records Dietary Practices Disease Eating Energy Intake Energy Metabolism Epidemic Epidemiology Event Fasting Glycosylated hemoglobin A Goals Health Health Care Costs Hormones Hour Indirect Calorimetry Individual Industry Intermittent fasting Intervention Knowledge Labor Unions Laboratories Laboratory Study Lead Measures Melatonin Mentored Research Scientist Development Award Mentors Metabolic Metabolic Diseases Metabolism Modeling Modernization Natural experiment Nature Obesity Occupational Occupations Overweight Persons Physical activity Population Procedures Prospective Studies Prospective cohort Protocols documentation Reporting Research Research Personnel Risk Risk Factors Sampling Schedule Scientist Services Sleep Societies Testing Thinness Time Training Travel United States Weight Weight Gain Work Workplace activity marker base cardiometabolism circadian circadian pacemaker combat cost dashboard design energy balance fast food food consumption improved metabolic rate novel occupational hazard prevent programs prospective shift work success trend

项目摘要

Project Summary/Abstract Weight gain and obesity have reached epidemic proportions in modern society. Obesity is a risk factor for numerous metabolic diseases and accounts for ~$147 billion in health care costs each year in the United States, thus making identification of mechanisms for obesity necessary for targeted interventions. In cross-sectional and controlled in-laboratory studies, eating during the night has been found to be a risk factor for weight gain and poor health, yet it is not known how the circadian timing (i.e., the timing of an event in relation to levels of a circadian marker) of food intake in real-world schedules may contribute to disease. In this epidemiological observational prospective cohort, we will elucidate potential circadian mechanisms for weight gain and cardiometabolic disease by studying a natural experiment that occurs when newly-hired transit bus operators transition from a day schedule to an early morning and/or late evening schedule. This allows a unique prospective examination, unlike previous cross-sectional observations, of how changing the circadian timing of food intake impacts energy balance behaviors (i.e., eating, activity, sleep) and cardiometabolic health in real-world settings. We have recently found that the closer an individual eats to their circadian night is associated with a higher percentage of body fat relative to weight. However, from an epidemiological perspective, it is difficult to disentangle the impact of eating at night on metabolism and weight gain through cross-sectional designs. We will utilize an occupational natural experiment in a prospective manner to identify how a rapid transition to eating during the circadian night (when the hormone melatonin is high) alters energy balance behaviors. Our preliminary data suggests new bus drivers gain ~7 pounds in their first year on the job, when they are forced to work at times (early morning or at night, both when melatonin concentrations are elevated) when their circadian clock is promoting fasting and sleep. For this observational prospective cohort, we will measures new drivers circadian timing (melatonin) and track the timing and content of food consumed for 3, 1-week episodes using a time- stamped mobile phone food diary during a pre-service training (baseline day-eating schedule), the first 30-days of driving (acute shift to eating during the circadian night), and at 90-days of driving. Cardiometablic health will be measured after each meal tracking episode. The specific aims of this proposal are to test the hypotheses that the transition to an early morning or late evening schedule will: 1) increase the percentage of daily calories new transit drivers consume, particularly carbohydrates, during the circadian night relative to baseline; 2) reduce energy expenditure through physical activity; and 3) be associated with poorer cardiometabolic health. To achieve my long-term goal of becoming an independent scientist conducting translational sleep and circadian research, this Mentored Research Scientist Development Award will provide further training in the following areas: 1) working with business organizations and labor unions; 2) field work; 3) implementing study procedures into a workplace setting; and 4) incorporation of epidemiological cardiometabolic variables and into research.

项目概要/摘要在现代社会，体重增加和肥胖已达到流行病的程度。肥胖是一个危险因素多种代谢疾病，每年在美国造成约 1,470 亿美元的医疗保健费用，因此，确定肥胖机制对于有针对性的干预措施是必要的。在横截面和受控的实验室研究发现，夜间进食是体重增加和体重增加的危险因素健康状况不佳，但尚不清楚昼夜节律（即事件的时间与生物钟水平的关系）如何现实世界时间表中的食物摄入量（昼夜节律标记）可能会导致疾病。在这次流行病学观察性前瞻性队列，我们将阐明体重增加的潜在昼夜节律机制通过研究新雇用的公交运营商时发生的自然实验来研究心脏代谢疾病从一天的时间表过渡到清晨和/或深夜的时间表。这使得一个独特的前景与之前的横断面观察不同，检查如何改变食物摄入的昼夜节律时间影响现实世界中的能量平衡行为（即饮食、活动、睡眠）和心脏代谢健康。我们最近发现，一个人的饮食越接近其昼夜节律，其睡眠质量越高。身体脂肪相对于体重的百分比。但从流行病学角度来看，很难通过横截面设计阐明夜间进食对新陈代谢和体重增加的影响。我们将前瞻性地利用职业自然实验来确定如何快速过渡到饮食在昼夜节律夜间（褪黑激素水平较高时）会改变能量平衡行为。我们的初步数据显示，新公交车司机在工作第一年体重增加了约 7 磅，因为他们有时被迫工作（清晨或晚上，褪黑激素浓度升高）当他们的生物钟处于促进禁食和睡眠。对于这个观察性前瞻性队列，我们将测量新驾驶员的昼夜节律计时（褪黑激素）并使用 time- 跟踪 3 个、1 周的发作中消耗食物的时间和内容- 职前培训期间在手机上盖章的饮食日记（基准日饮食计划），前 30 天驾驶期间（昼夜节律夜间急剧转向进食）以及驾驶 90 天时的情况。心脏代谢健康将每次进餐跟踪后进行测量。该提案的具体目的是检验以下假设：过渡到清晨或傍晚的时间表将：1）增加每日新卡路里的百分比相对于基线，公交司机在夜间昼夜节律期间的消耗量，尤其是碳水化合物的消耗量； 2）减少通过体力活动消耗能量； 3) 与较差的心脏代谢健康有关。为了实现我的长期目标，成为一名进行转化睡眠和昼夜节律研究的独立科学家研究，该指导研究科学家发展奖将提供以下方面的进一步培训领域： 1）与商业组织和工会合作； 2）现场工作； 3）实施研究程序进入工作场所环境； 4) 将流行病学心脏代谢变量纳入研究。