Metabolic Effects of Sleep Extension in People with Obesity

项目总结/摘要 流行病学和睡眠干预研究的数据都表明，睡眠不足 导致代谢功能障碍，并与肥胖风险增加有关 和代谢疾病，如2型糖尿病（T2 D）。然而，全面 对睡眠延长的潜在治疗益处的评估尚未在 人这项建议的总体目标是确定睡眠延长对多方面的影响， 系统代谢功能和潜在的机制之间的联系负责 睡眠不足和代谢功能障碍，包括昼夜节律失调， 氧化应激、血浆代谢组学以及全身和脂肪组织炎症， 习惯性保持慢性短睡眠的代谢不健康肥胖（MUO）人群 时间表。因此，我们组建了一个跨学科的研究团队， 代谢（S. Klein，G.史密斯在华盛顿大学医学院[WUSM]），睡眠（K。 科罗拉多大学博尔德分校的布鲁萨尔和B。Lucey [WUSM]），昼夜节律生物学 和分子科学（J. Yoshino [WUSM]），和代谢组学（M.耆那教 加州圣地亚哥）进行随机对照试验，以评估6周的睡眠延长 对MUO患者进行干预，这些人习惯性睡眠≤6.0 h/night。我们将确定 睡眠延长，对：1）多器官胰岛素敏感性（通过使用两阶段 高胰岛素-正葡萄糖钳夹术联合稳定同位素示踪剂），2）24小时 血浆葡萄糖、游离脂肪酸和激素谱，和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 负责睡眠不足引起的代谢功能障碍，通过靶向（昼夜节律 失调、时钟基因、炎症和氧化应激）和非靶向（质量 光谱驱动的代谢组）方法。这项跨学科研究的结果 合作将提供重要的见解，了解生理和分子 睡眠和代谢功能之间的相互作用，并可以为睡眠提供证据。 作为改善高风险人群代谢健康的对策， 代谢性疾病

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.