Drosophila insulin-like peptide 2 mediates dietary regulation of sleep intensity

Abstract

Sleep is a nearly universal behavior that is regulated by diverse environmental and physiological stimuli. A defining feature of sleep is a homeostatic rebound following deprivation, where animals compensate for lost sleep by increasing sleep duration and/or sleep depth. Fruit flies exhibit robust recovery sleep following deprivation and represent a powerful model to study neural circuits regulating sleep homeostasis. Numerous neuronal populations have been identified in modulating sleep homeostasis as well as depth, raising the possibility that recovery sleep is differentially regulated by environmental or physiological processes that induce sleep deprivation. Here, we find that unlike most pharmacological and environmental manipulations commonly used to restrict sleep, starvation potently induces sleep loss without a subsequent rebound in sleep duration or depth. We find that both starvation and a sucrose-only diet result in reduced metabolic rate and increased sleep depth, suggesting that dietary yeast protein is essential for normal sleep depth and homeostasis. Finally, we find that Drosophila insulin like peptide 2 (Dilp2) is required for starvation-induced changes in sleep depth without regulating the duration of sleep. Remarkably, Dilp2 mutant flies require rebound sleep following sleep deprivation, suggesting Dilp2 underlies resilience to sleep loss. Together, these findings reveal innate resilience to starvation-induced sleep loss and identify distinct mechanisms that underlie starvation-induced changes in sleep duration and depth.\n\nAuthor SummarySleep is nearly universal throughout the animal kingdom and homeostatic regulation represents a defining feature of sleep, where animals compensate for lost sleep by increasing sleep over subsequent time periods. Despite the robustness of this feature, surprisingly little is known about how recovery-sleep is regulated in response to different types of sleep deprivation. Fruit flies provide a powerful model for investigating the genetic regulation of sleep, and like mammals, display robust recovery sleep following deprivation. Here, we find that unlike most stimuli that suppress sleep, sleep deprivation by starvation does not require a homeostatic rebound. These findings appear to be due to flies engaging in deeper sleep during the period of partial deprivation, suggesting a natural resilience to starvation-induced sleep loss. This unique resilience to starvation-induced sleep loss is dependent on Drosophila insulin-like peptide 2, suggesting a critical role for insulin signaling in regulating interactions between diet and sleep homeostasis.