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.

项目总结/文摘