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：
8852702
负责人：
FRANK A SCHEER
金额：
$ 63.75万
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/8852702
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 cardiometabolic risk circadian pacemaker clinically relevant design diabetes risk feeding feeding schedule insight novel therapeutic intervention obesity risk prevent shift work success tocol

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：轮班工作会增加患糖尿病、肥胖症和心血管疾病的风险，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，昼夜节律失调，即中央昼夜节律起搏器与行为睡眠/觉醒周期（这在轮班工人中很常见）之间的失调，在保持热量摄入和体力活动恒定的同时，会导致不利的代谢变化。这些发现可能有助于解释轮班工作对健康造成的不利后果。最近，我们还在一项前瞻性研究中证明，进餐时间可以预测减肥治疗的成功，与热量摄入、活动和睡眠时间无关。进餐时间的重要性与动物实验工作一致，表明使禁食/进食周期的昼夜节律时间正常化（不使睡眠/觉醒周期正常化）可以防止这种不利的代谢影响。此外，中央起搏器与禁食/进食周期之间的错位导致中央昼夜节律起搏器与身体其他部位的外周昼夜节律振荡器之间的不同步，特别是在肝脏和胰腺等代谢器官中，这种现象被称为“内部不同步” ，这可能与昼夜节律失调的不良代谢后果有关。然而，迄今为止，还没有证据支持或反对人类内部不同步的发展，这可能是因为测试该假设所需的严格且复杂的昼夜节律方案。在当前的提案中，我们将测试控制食物摄入时间是否可以防止昼夜节律失调的不利代谢影响（目标 1），以及中央昼夜节律起搏器和行为周期之间的不同步是否会导致人类内部不同步（目标 2）。由于从事轮班工作的劳动力比例很高且后果严重，该提案具有很大的临床意义，并为以后开发一种新的治疗方法来应对慢性慢性病易感人群心脏代谢疾病风险增加奠定科学基础。接触。