Dietary and Endocrine Regulation of Sleep

建议书摘要 动物会敏锐地调整自己的行为以适应环境的变化。食物的缺乏 代表了一种常见的环境挑战，需要行为和代谢适应。动物 对饥饿的反应是通过抑制睡眠来寻找食物。这种饥饿诱导的睡眠 抑制涉及内分泌系统之间的通信，这些内分泌系统在 脂肪组织和大脑。果蝇，果蝇，像哺乳动物一样，按顺序抑制睡眠 寻找食物，并利用许多保守的分子途径，包括胰岛素和类胰高血糖素 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和 苍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，以阐明新陈代谢调节的一般机制 行为。PI的初步数据表明，果蝇胰岛素和类胰高血糖素的作用 当食物有限时，荷尔蒙(AKH)控制睡眠的途径。这些发现导致了假设 胰岛素和AKH信号改变营养水平以诱导动物改变其行为 相应地。为了解决这一假设，我们将确定正常睡眠所需的代谢底物(S) 通过饮食和药物对营养储备的操纵。此外，这项提案寻求 确定胰岛素和AKH信号控制饥饿诱导的睡眠抑制和 无论这是通过营养储存的长期变化还是通过对脂肪身体功能的急性调节而发生的。 总而言之，这项研究计划使用行为和代谢分析来检查 组织类型感知饥饿并进行交流，以启动适应行为。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，并提供对 新陈代谢相关疾病的潜在基础。 PHS 398/2590(版本06/09)项目摘要/摘要页

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