Uncovering Circadian Mechanisms of Poor Cardiometabolic Health

项目摘要/摘要 在现代社会，体重增加和肥胖已经达到了流行的程度。肥胖是一种危险因素 许多代谢性疾病，在美国每年造成约1470亿美元的医疗费用， 因此，确定肥胖的机制对于有针对性的干预是必要的。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 健康状况不佳，但目前尚不清楚昼夜节律计时(即事件的计时与 在现实生活中，食物摄入量的昼夜节律)可能会导致疾病。在这场流行病学调查中 观察性前瞻性队列，我们将阐明潜在的昼夜节律机制体重增加和 心脏代谢性疾病研究了一项自然实验，这项实验发生在新雇用的公交运营商 从白天的日程安排过渡到清晨和/或傍晚的日程安排。这允许一个独特的前景 与以前的横断面观察不同，检查如何改变食物摄入量的昼夜节律 在真实环境中影响能量平衡行为(即饮食、活动、睡眠)和心脏代谢健康。 我们最近发现，一个人吃得越接近他们昼夜节律的时间，就会产生更高的 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，很难 通过横断面设计，理清夜间进食对新陈代谢和体重增加的影响。我们 将以一种前瞻性的方式利用职业性自然实验来确定快速过渡到饮食 在昼夜(褪黑激素水平较高的时候)会改变能量平衡行为。我们的预赛 数据显示，新的公交车司机在工作的第一年会增加大约7磅，因为他们有时会被迫工作 (清晨或夜间，当褪黑激素浓度升高时)当它们的生物钟 提倡禁食和睡眠。对于这个观察性的前瞻性队列，我们将测量新的驾驶员昼夜节律 计时(褪黑素)，并使用时间-跟踪3，1周发作的食物摄入的时间和内容- 在职前培训期间盖章的手机食物日记(基线进食时间表)，头30天 开车(在昼夜里突然转向吃东西)，以及90天的驾驶。心脏代谢健康意愿 在每一次用餐跟踪节目之后进行测量。这项提议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)增加每日卡路里的百分比 与基线相比，公交司机在昼夜节律的夜间消耗，尤其是碳水化合物；2)减少 通过体力活动消耗能量；3)心脏新陈代谢健康状况较差。 为了实现我的长期目标，成为一名从事翻译睡眠和昼夜节律的独立科学家 研究，这个指导性研究科学家发展奖将在以下方面提供进一步的培训 领域：1)与企业组织和工会合作；2)实地工作；3)实施学习程序 纳入工作场所环境；以及4)纳入流行病学心脏代谢变量并纳入研究。

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.