Dietary and Endocrine Regulation of Sleep

描述(由申请者提供)：动物被敏锐地调整以适应它们的行为以适应环境的变化。缺乏食物是一种常见的环境挑战，需要行为和新陈代谢适应。动物对饥饿的反应是抑制睡眠，以便觅食。这种饥饿导致的睡眠抑制涉及内分泌系统之间的通信，内分泌系统负责传递脂肪组织和大脑之间的营养供应。果蝇，黑腹果蝇，像哺乳动物一样，为了觅食而抑制睡眠，并利用许多保守的分子途径，包括胰岛素和胰高血糖素样信号来控制动态平衡和新陈代谢。由于果蝇和哺乳动物之间的代谢系统和行为高度保守，这里概述的实验将提供适用于果蝇以外的生物学信息，以阐明新陈代谢调节行为的一般机制。来自PI的初步数据表明，当食物有限时，果蝇胰岛素和胰升糖素样激素(AKH)途径在控制睡眠方面发挥了作用。这些发现导致了一种假设，即胰岛素和AKH信号会改变营养水平，从而诱导动物相应地改变其行为。为了解决这一假设，正常睡眠所需的代谢底物(S)将通过营养储存的饮食和药物操作来确定。此外，这项建议试图确定胰岛素和AKH信号控制饥饿诱导的睡眠抑制的机制，以及这是通过营养储备的长期变化还是通过对脂肪身体功能的急性调节来实现的。总而言之，这项研究计划使用行为和新陈代谢分析来检查不同的组织类型是如何感觉饥饿和沟通以启动适应行为的。这些实验将进一步加深我们对新陈代谢如何调节行为的理解，并为新陈代谢相关疾病的潜在基础提供洞察。

DESCRIPTION (provided by applicant): Animals are keenly tuned to adapt their behavior in response to environmental changes. The absence of food represents a common environmental challenge that requires behavioral and metabolic adaptation. Animals respond to starvation by suppressing sleep in order to forage for food. This starvation-induced sleep suppression involves communication between endocrine systems that relay nutrient availability between adipose tissue and the brain. The fruit fly, Drosophila melanogaster, like mammals, suppresses sleep in order to forage for food and utilizes many conserved molecular pathways including insulin and glucagon-like signaling to control homeostasis and metabolism. Due to the high conservation of metabolic systems and behavior between flies and mammals, the experiments outlined here will provide biological information applicable beyond the fruit fly to elucidate the general mechanisms through which metabolism regulates behavior. Preliminary data from the PIs indicates a role for the Drosophila insulin and the glucagon-like hormone (AKH) pathways in controlling sleep when food is limited. These findings led to the hypothesis that insulin and AKH signal changes in nutrient levels to induce the animal to alter its behavior accordingly. To address this hypothesis, the metabolic substrate(s) required for normal sleep will be identified through dietary and pharmacological manipulation of nutrient stores. Additionally, this proposal seeks to determine the mechanisms whereby insulin and AKH signaling control hunger-induced sleep suppression and whether this occurs through long-term changes in nutrient stores or acute regulation of fat body function. Taken together, this research plan employs behavioral and metabolic analysis to examine how distinct tissue types sense hunger and communicate to initiate adaptive behavior. These experiments wil further our understanding of how metabolism regulates behavior and provide insight into the underlying basis of metabolism-linked disorders.