Dietary and Endocrine Regulation of Sleep

提案摘要 动物敏锐地调整自己的行为以适应环境的变化。缺乏食物 代表了一种常见的环境挑战，需要行为和代谢适应。动物 通过抑制睡眠以寻找食物来应对饥饿。这种饥饿导致的睡眠 抑制涉及内分泌系统之间的通信， 脂肪组织和大脑果蝇和哺乳动物一样， 觅食，并利用许多保守的分子途径，包括胰岛素和胰高血糖素样 控制体内平衡和新陈代谢的信号。由于代谢系统的高度保守性， 为了研究果蝇和哺乳动物之间的行为，这里概述的实验将提供生物学信息， 适用于果蝇以外的阐明代谢调节的一般机制 行为来自PI的初步数据表明果蝇胰岛素和胰高血糖素样肽的作用。 激素（AKH）通路在控制睡眠时，食物是有限的。这些发现引出了一个假设 胰岛素和AKH信号在营养水平的变化，诱导动物改变其行为 相应地为了解决这一假设，将确定正常睡眠所需的代谢底物 通过饮食和药物控制营养物质的储存。此外，该提案旨在 确定胰岛素和AKH信号传导控制饥饿诱导的睡眠抑制的机制， 无论这是通过营养储存的长期变化还是脂肪体功能的急性调节而发生的。 总之，这项研究计划采用行为和代谢分析，以研究如何不同的 组织类型感知饥饿并进行交流以启动适应性行为。这些实验将 进一步了解新陈代谢如何调节行为，并提供洞察 代谢相关疾病的潜在基础。 PHS 398/2590（2009年6月修订版）

Proposal Summary 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 will further our understanding of how metabolism regulates behavior and provide insight into the underlying basis of metabolism-linked disorders. PHS 398/2590 (Rev. 06/09) Page Project Summary/Abstract