Uncovering Circadian Mechanisms of Poor Cardiometabolic Health

项目概要/摘要 体重增加和肥胖在现代社会已达到流行病的程度。肥胖是一个危险因素， 在美国，许多代谢性疾病每年造成约1470亿美元的医疗保健费用， 因此，确定肥胖症的机制是有针对性的干预措施所必需的。在横截面和 对照实验室研究发现，夜间进食是体重增加的危险因素， 健康状况不佳，但不知道昼夜节律定时（即，事件发生的时间与 在现实世界的时间表中，食物摄入的昼夜节律标志物）可能导致疾病。在这场流行病学 观察性前瞻性队列，我们将阐明体重增加的潜在昼夜机制， 通过研究一项自然实验，新雇用的公交车运营商 从白天时间表到清晨和/或深夜时间表的转换。这使得一个独特的前景 与以前的横断面观察不同，研究如何改变食物摄入的昼夜节律 影响能量平衡行为（即，饮食，活动，睡眠）和心脏代谢健康在现实世界的设置。 我们最近发现，一个人吃得越接近他们的昼夜节律， 身体脂肪相对于体重的百分比。然而，从流行病学的角度来看， 通过横截面设计，解开夜间进食对新陈代谢和体重增加的影响。我们 我将以前瞻性的方式利用职业自然实验，以确定如何快速过渡到吃 在昼夜节律的夜晚（当褪黑激素高时）改变能量平衡行为。我们的初步 数据显示，新的公共汽车司机在工作的第一年会增加7磅，因为他们有时被迫工作。 （清晨或晚上，当褪黑激素浓度升高时）当他们的生物钟 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， 定时（褪黑激素），并使用时间- 在服务前培训期间（基线日进食时间表），前30天，在移动的手机上打印食物日记 驾驶（在昼夜节律的夜晚急性转变为进食），以及驾驶90天。心脏代谢健康将 在每次用餐跟踪事件后进行测量。本提案的具体目的是检验以下假设： 转换到清晨或深夜的时间表将：1）增加每日卡路里的百分比， 运输司机消耗，特别是碳水化合物，在昼夜节律的夜晚相对于基线; 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，成为一名独立的科学家， 研究，这个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）实地工作; 3）执行研究程序 纳入工作场所的设置;和4）纳入流行病学心脏代谢变量和研究。

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.