Metabolic Effects of Sleep Extension in People with Obesity

延长睡眠对肥胖者的代谢影响

• 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
• 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

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.

项目摘要/摘要 流行病学和睡眠干预研究的数据表明睡眠不足 引起代谢功能障碍，并与肥胖的风险增加有关 和代谢疾病，例如2型糖尿病（T2D）。但是，这是一个全面的 评估睡眠扩展的潜在理论益处尚未评估 人们。该提案的总体目标是确定睡眠延长对多种的影响 系统代谢功能和负责联系的潜在机制 睡眠不足和代谢功能障碍，包括昼夜节律，增加了 氧化应激，血浆代谢组学以及全身性和脂肪组织注射 患有代谢不健康的肥胖症（MUO）的人，他们习惯保持慢性睡眠 时间表。彼此之间，我们组建了一个具有专业知识的跨学科研究团队 代谢（S. 赖特（Wright），科罗拉多大学博尔德分校和B. lucey [wusm] 和分子科学（J. Yoshino [WUSM]）和代谢组学（大学的M. Jain 加利福尼亚州圣地亚哥）进行一项随机对照试验，以评估6周睡眠扩展 干预习惯性睡眠≤6.0h/night的MUO的人。我们将确定效果 睡眠扩展，on：1）多器官胰岛素灵敏度（通过使用两阶段进行评估 高胰岛素血糖夹具与稳定的同位素示踪剂结合），2）24H 血浆葡萄糖，游离脂肪酸和马烯轮廓，以及3）肝内甘油三酸酯含量 （通过使用磁共振成像评估）和潜在的细胞机制 通过靶向的（昼夜节律）负责睡眠引起的代谢功能障碍不足 未对准，时钟基因，炎症和氧化应激）和非目标（质量） 光谱驱动的代谢组方法。这个跨学科的结果 协作将为理解物理和分子提供重要的见解 睡眠和代谢功能之间的相互作用，可以为睡眠提供证据 扩展作为改善发展高风险的代谢健康的对策 代谢疾病。