Dietary and Endocrine Regulation of Sleep

描述（由申请人提供）：动物敏锐地调整自己的行为以应对环境的变化。缺乏食物是一种共同的环境挑战，需要行为和代谢适应。动物对饥饿的反应是抑制睡眠以寻找食物。这种由饥饿引起的睡眠抑制涉及到在脂肪组织和大脑之间传递营养可用性的内分泌系统之间的交流。果蝇（Drosophila melanogaster）和哺乳动物一样，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体内平衡和代谢。由于果蝇和哺乳动物之间代谢系统和行为的高度保守性，这里概述的实验将提供适用于果蝇以外的生物学信息，以阐明代谢调节行为的一般机制。来自pi的初步数据表明，果蝇胰岛素和胰高血糖素样激素（AKH）通路在食物受限时控制睡眠中起作用。这些发现导致了胰岛素和AKH信号在营养水平上的变化，从而诱导动物相应地改变其行为的假设。为了解决这一假设，正常睡眠所需的代谢底物将通过营养储存的饮食和药理操作来确定。此外，本研究旨在确定胰岛素和AKH信号控制饥饿引起的睡眠抑制的机制，以及这是否通过营养储存的长期变化或脂肪体功能的急性调节发生。综上所述，本研究计划采用行为和代谢分析来研究不同类型的组织如何感知饥饿并进行沟通以启动适应性行为。这些实验将进一步加深我们对代谢如何调节行为的理解，并为代谢相关疾病的潜在基础提供见解。

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.