Metabolic Effects of Sleep Extension in People with Obesity

延长睡眠对肥胖者的代谢影响

基本信息

批准号：
10201581
负责人：
Samuel Klein
金额：
$ 60.77万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201581
关键词：
Adipose tissue Admission activity Beds Binding Biology Biopsy Blood Glucose Blood specimen Body Weight Body mass index California Cardiometabolic Disease Chronic Circadian Dysregulation Circadian Rhythms Circadian desynchrony Collection Colorado Complex Data Energy Intake Ensure Epidemiology Event Fatty acid glycerol esters Future Gene Expression Genes Glucose Glucose Clamp Glucose Intolerance Glutathione Glutathione Disulfide Goals Health Home Hormones Hour Impaired fasting glycaemia Inflammation Infusion procedures Inpatients Insulin Insulin Resistance Intervention Intervention Studies Investigation Link Lipolysis Liver Magnetic Resonance Imaging Mass Spectrum Analysis Measurement Melatonin Metabolic Metabolic Diseases Metabolic dysfunction Metabolism Molecular Muscle Narcolepsy Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Obesity Outcome Oxidative Stress Participant Peripheral Peripheral Blood Mononuclear Cell Physiological Plasma Polysomnography Prediabetes syndrome Procedures Prostaglandins Proteins Randomized Randomized Controlled Trials Research Research Personnel Resistance development Risk Schedule Science Sleep Sleep Apnea Syndromes Sleep Deprivation Sleep Disorders Sleeplessness Testing Therapeutic Therapeutic Effect Time Tracer Triglycerides Universities Urine Washington Wrist actigraphy adult obesity attentional control circadian circadian pacemaker clinically significant cytokine glucose disposal glucose production high risk improved in vivo inflammatory marker insight insulin sensitivity interdisciplinary collaboration intrahepatic medical schools metabolome metabolomics novel sleep pattern stable isotope suprachiasmatic nucleus urinary

项目摘要

Project Summary/Abstract Data from both epidemiological and sleep intervention studies have shown that insufficient sleep causes metabolic dysfunction and is associated with an increased risk of developing obesity and metabolic diseases, such as type 2 diabetes (T2D). However, a comprehensive assessment of the potential therapeutic benefits of sleep extension have not been evaluated in people. The overall goal of this proposal is to determine the effect of sleep extension on multi- system metabolic function and the potential mechanisms responsible for the link between insufficient sleep and metabolic dysfunction, including circadian misalignment, increased oxidative stress, plasma metabolomics and both systemic and adipose tissue inflammation in people with metabolically unhealthy obesity (MUO) who habitually maintain chronic short sleep schedules. Accordingly, we have assembled a transdisciplinary research team with expertise in metabolism (S. Klein, G. Smith at Washington University School of Medicine [WUSM]), sleep (K. Wright, J. Broussard at University of Colorado Boulder and B. Lucey [WUSM]), circadian biology and molecular science (J. Yoshino [WUSM]), and metabolomics (M. Jain at University of California San Diego) to conduct a randomized controlled trial to assess a 6-wk sleep extension intervention in people with MUO, who habitually sleep ≤6.0 h/night. We will determine the effect of sleep extension, on: 1) multi-organ insulin sensitivity (assessed by using the two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracers), 2) 24h plasma glucose, free fatty acids and hormone profiles, and 3) intrahepatic triglyceride content (assessed by using magnetic resonance imaging) and the potential cellular mechanisms responsible for insufficient sleep-induced metabolic dysfunction, by targeted (circadian misalignment, clock genes, inflammation, and oxidative stress) and non-targeted (mass spectroscopy-driven metabolome) approaches. The results from this transdisciplinary collaboration will provide important insights into understanding the physiological and molecular interactions between sleep and metabolic function, and could provide evidence for sleep extension as a countermeasure to improve metabolic health in people at high risk for developing metabolic diseases.

项目概要/摘要流行病学和睡眠干预研究的数据均表明，睡眠不足导致代谢功能障碍，并与肥胖风险增加相关和代谢疾病，例如 2 型糖尿病 (T2D)。尚未对延长睡眠的潜在治疗益处进行评估该提案的总体目标是确定延长睡眠对多人的影响。系统代谢功能和负责之间联系的潜在机制睡眠不足和代谢功能障碍（包括昼夜节律失调）增加氧化应激、血浆代谢组学以及全身和脂肪组织炎症患有代谢不健康肥胖症 (MUO) 且习惯性长期睡眠不足的人因此，我们组建了一支具有专业知识的跨学科研究团队。新陈代谢（华盛顿大学医学院 [WUSM] 的 S. Klein、G. Smith）、睡眠（K. Wright、科罗拉多大学博尔德分校的 J. Broussard 和 B. Lucey [WUSM]），昼夜节律生物学。和分子科学（J. Yoshino [WUSM]）和代谢组学（M. Jain）加利福尼亚州圣地亚哥）进行一项随机对照试验来评估延长 6 周的睡眠时间对习惯性睡眠≤6.0 小时/晚的 MUO 患者进行干预，我们将确定效果。睡眠延长的影响，关于：1）多器官胰岛素敏感性（通过使用两阶段评估高胰岛素-正常血糖钳夹程序与稳定同位素示踪剂结合使用), 2) 24 小时血浆葡萄糖、游离脂肪酸和激素谱，以及 3) 肝内甘油三酯含量（通过使用磁共振成像评估）和潜在的细胞机制睡眠不足引起的代谢功能障碍的原因，通过有针对性的（昼夜节律）错位、时钟基因、炎症和氧化应激）和非靶向（质量这种跨学科方法的结果。合作将为理解生理和分子生物学提供重要的见解睡眠与代谢功能之间的相互作用，可为睡眠提供证据扩展作为改善高风险人群代谢健康的对策代谢性疾病。