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Development of countermeasures against adverse metabolic effects of shift work

针对轮班工作对代谢的不良影响制定对策

基本信息

批准号：
8630702
负责人：
FRANK A SCHEER
金额：
$ 64.57万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8630702
关键词：
Address Animals Automobile Driving Behavioral Biological Body Weight decreased Cardiovascular Diseases Chronic Circadian Rhythms Complex Development Diabetes Mellitus Diet Disease Dissociation Eating Energy Intake Exposure to FarGo Fasting Foundations Glucose Health Human Lead Leptin Life Life Style Light Liver Melatonin Metabolic Metabolic Marker Obesity Organ Pacemakers Pancreas Participant Peripheral Phase Physical activity Prospective Studies Protocols documentation Publishing Research Rest Risk Rodent Role Schedule Sleep Sleep Wake Cycle Slow-Wave Sleep Socioeconomic Status Sterile coverings Testing Time Training Tweens Vulnerable Populations Work circadian pacemaker clinically relevant design diabetes risk feeding feeding schedule insight novel therapeutic intervention obesity risk prevent public health relevance shift work success tocol

项目摘要

Abstract Shift work is associated with an increased risk for the development of diabetes, obesity, and cardiovascular disease, which cannot be fully explained by differences in life style and socioeconomic status. Recently, we demonstrated that circadian misalignment, the misalignment between the central circadian pacemaker and the behavioral sleep/wake cycle (that is typical in shift workers), while keeping caloric intake and physical activity constant, leads to adverse metabolic changes. These findings may help explain the adverse health consequences of shift work. More recently, we also demonstrated in a prospective study that the timing of meals predicts the success of weight loss therapy, independent of caloric intake, activity and sleep duration. The importance of meal timing is consistent with animal experimental work showing that normalizing the circadian timing of the fasting/feeding cycle (without normalizing the sleep/wake cycle) prevents such adverse metabolic effects. Furthermore, misalignment between the central pacemaker and the fasting/feeding cycle leads to desynchrony between the central circadian pacemaker and peripheral circadian oscillators in the rest of the body, especially in metabolic organs such as liver and pancreas, a phenomenon known as "internal desynchrony", which may relate to the adverse metabolic consequences of circadian misalignment. However, to date there exists no evidence for or against the development of internal desynchrony in humans, likely because of the demanding and complex circadian protocols required to test that hypothesis. In the current proposal, we will test whether manipulating the timing of food intake prevents the adverse metabolic effects of circadian misalignment (Aim 1), and whether desynchrony between the central circadian pacemaker and the behavioral cycle leads to internal desynchrony in humans (Aim 2). Because of the high proportion of the work force exposed to shift work and the grave consequences, this proposal has great clinical relevance and lays the scientific foundation for later development of a novel therapeutic approach against the increased risk for cardiometabolic disorders in this vulnerable population with chronic exposure.

摘要倒班工作会增加患糖尿病、肥胖症和心血管疾病的风险疾病，这不能用生活方式和社会经济地位的差异来完全解释。最近，我们证明了昼夜节律失调，中央昼夜节律起搏器和行为睡眠/清醒周期(这在倒班工人中是典型的)，同时保持卡路里摄入量和体力活动恒定，导致不利的新陈代谢变化。这些发现可能有助于解释不利的健康状况。倒班工作的后果。最近，我们还在一项前瞻性研究中证明，膳食预测减肥疗法的成功，与卡路里摄入量、活动和睡眠时间无关。进食时间的重要性与动物实验工作相一致，表明将禁食/进食周期的昼夜节律(没有使睡眠/清醒周期正常化)防止了这种不利的情况新陈代谢影响。此外，中央起搏器和禁食/喂食周期之间的不对准导致中央昼夜节律起搏器和周围昼夜节律振荡器之间的去同步性体内的，尤指肝脏和胰腺等新陈代谢器官，这种现象被称为“体内去同步化“，这可能与昼夜节律失调的不利代谢后果有关。然而，到目前为止，没有证据支持或反对人类内部去同步化的发展，很可能因为检验这一假说需要严格而复杂的昼夜节律。在当前建议，我们将测试控制食物摄取的时间是否可以防止昼夜节律失调(目标1)，以及中央昼夜节律起搏器和行为周期导致人类内部的去同步化(目标2)。因为这项工作的比例很高暴露在倒班工作中的力量和严重后果，这一建议具有很大的临床意义和铺垫为以后开发一种新的治疗方法以对抗增加的风险奠定了科学基础长期暴露在这一脆弱人群中的心脏代谢障碍。