Shortened sleep and food motivation: hypothalamic and striatal substrates

描述（由申请人提供）： 目前的肥胖“流行病”已被称为全球主要的公共卫生问题之一;然而，所有的因素诱发个人肥胖尚未确定。现在有临床研究的挑衅性证据表明，睡眠时间缩短会导致肥胖表型，鉴于平均睡眠时间在过去50年中减少了20%，这是一个特别令人担忧的发现。 为了探索睡眠限制和肥胖之间联系的生理机制，我们制定了一项研究计划，旨在研究睡眠时间缩短对参与食物摄入中枢控制的三个主要神经化学系统的影响：下丘脑中底轴（参与将外周能量平衡信号转化为行为），下丘脑-垂体-肾上腺轴（可能与压力诱导的对高能量食物的偏好有关），以及纹状体阿片和多巴胺系统（介导与食物动机有关的高阶过程）。我们还提出了一个详细的分析睡眠限制对摄食行为的关键动机和结构组成部分的影响，包括喂养微观结构，风味和宏量营养素的偏好，以及食物奖励。该提案的一个独特之处在于，该创新系统将用于精确限制睡眠，并直接在设备本身内记录摄食行为的几个组成部分。此外，我们将使用一种新的时间表，轻度睡眠限制分开的恢复期，一种方法，可能有更大的面子和结构效度比以前的范例中使用的文献。 与公共卫生的相关性：这些研究有可能精确地确定睡眠缩短可能导致肥胖风险增加的神经，内分泌和行为机制。到目前为止，这些因素知之甚少，以前曾使用不反映人类状况的睡眠剥夺时间表进行研究。了解睡眠缩短和肥胖之间的机制联系可能会导致新的策略/药物靶点，有助于减少肥胖流行，从而有望降低心血管疾病和2型糖尿病的发病率。

DESCRIPTION (provided by applicant): The current 'epidemic' of obesity has been called one of the leading public health concerns worldwide; nevertheless, all of the factors predisposing individuals to obesity have not been identified. There is now provocative evidence from clinical studies that shortened sleep duration can lead to an obese phenotype, a particularly alarming finding given that that average sleep duration has decreased by 20% over the last 50 years. To explore the physiological mechanisms underlying the link between sleep restriction and obesity, we have developed a research plan designed to study the impact of shortened sleep duration on three major neurochemical systems involved in the central control of food intake: the mediobasal hypothalamic axis (involved in translating peripheral energy balance signals into behavior), the hypothalamic-pituitary-adrenal axis (which may be involved in stress-induced preferences for energy-dense foods), and striatal opioid and dopamine systems (which mediate higher-order processes related to food motivation). We also propose a detailed analysis of sleep restriction effects on key motivational and structural components of ingestive behavior, including feeding microstructure, flavor and macronutrient preference, and food reward. A unique feature of this proposal is the novel, innovative system that will be used to precisely restrict sleep and record several components of ingestive behavior directly within the apparatus itself. In addition, we will use a novel schedule of mild sleep restriction separated by periods of recovery, a method that may have greater face and construct validity than previous paradigms used in the literature. Relevance to public health: These studs have the potential to precisely identify the neural, endocrine, and behavioral mechanisms by which sleep curtailment may lead to increased risk for obesity. To date, these factors are poorly understood, and have been previously studied using sleep deprivation schedules that do not reflect the human condition. Understanding the mechanistic link between shortened sleep and obesity may lead to novel strategies/drug targets that could help curtail the obesity epidemic, and thereby hopefully reduce rates of cardiovascular disease and type 2 diabetes.