Animals are keenly tuned to adapt their behavior in response to environmental changes. The absence of foodrepresents a common environmental challenge that requires behavioral and metabolic adaptation. Animalsrespond to starvation by suppressing sleep in order to forage for food. This starvation-induced sleepsuppression involves communication between endocrine systems that relay nutrient availability betweenadipose tissue and the brain. The fruit fly, Drosophila melanogaster, like mammals, suppresses sleep in orderto forage for food and utilizes many conserved molecular pathways including insulin and glucagon-likesignaling to control homeostasis and metabolism. Due to the high conservation of metabolic systems andbehavior between flies and mammals, the experiments outlined here will provide biological informationapplicable beyond the fruit fly to elucidate the general mechanisms through which metabolism regulatesbehavior. Preliminary data from the PIs indicates a role for the Drosophila insulin and the glucagon-likehormone (AKH) pathways in controlling sleep when food is limited. These findings led to the hypothesisthat insulin and AKH signal changes in nutrient levels to induce the animal to alter its behavioraccordingly. To address this hypothesis, the metabolic substrate(s) required for normal sleep will be identifiedthrough dietary and pharmacological manipulation of nutrient stores. Additionally, this proposal seeks todetermine the mechanisms whereby insulin and AKH signaling control hunger-induced sleep suppression andwhether 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 distincttissue types sense hunger and communicate to initiate adaptive behavior. These experiments willfurther our understanding of how metabolism regulates behavior and provide insight into theunderlying basis of metabolism-linked disorders.PHS 398/2590 (Rev. 06/09) Page Project Summary/Abstract
; First; Middle): Keene; Alex C.Proposal NarrativeDysregulation of both sleep and feeding behaviors presents an enormous health burden throughout the world;and interactions between these two behaviors have many clinical manifestations that include obesity in short-sleeping individuals and sleep disturbances in the undernourished. The metabolic substrate(s) required fornormal 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 controlhunger-induced sleep suppression and whether this occurs through long-term changes in nutrient stores oracute regulation of fat body function.PHS 398/2590 (Rev. 06/09) Page Project Narrative
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