Shortened sleep and food motivation: hypothalamic and striatal substrates

描述(由申请人提供)： 目前肥胖症的流行被称为全球主要的公共卫生问题之一；然而，所有导致个人肥胖的因素都还没有确定。现在有来自临床研究的具有挑衅性的证据表明，睡眠时间缩短会导致肥胖表型，这一发现特别令人震惊，因为在过去50年中，平均睡眠时间减少了20%。 为了探索睡眠限制和肥胖之间潜在的生理机制，我们制定了一项研究计划，旨在研究睡眠时间缩短对参与中央控制食物摄入的三个主要神经化学系统的影响：下丘脑内侧基底轴(参与将外周能量平衡信号转换为行为)，下丘脑-垂体-肾上腺轴(可能参与压力诱导的对高能量食物的偏好)，以及纹状体阿片和多巴胺系统(调节与食物动机相关的高级过程)。我们还建议详细分析睡眠限制对摄食行为的关键动机和结构成分的影响，包括摄食微结构、味道和常量营养素偏好以及食物奖励。这项提议的一个独特特点是，这个新颖、创新的系统将被用来精确地限制睡眠，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轻度睡眠限制时间表，将其按恢复期分开，这种方法可能比文献中使用的以前的范例更有面子和更具结构效度。 与公众健康相关：这些螺柱有可能准确地识别神经、内分泌和行为机制，通过这些机制，睡眠减少可能导致肥胖风险增加。到目前为止，人们对这些因素知之甚少，以前曾使用不能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带来新的策略/药物靶点，有助于遏制肥胖症的流行，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.