Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster

Shah

Faville³

et al. 2020

PLoS Genet

Sleep is a nearly universal behavior that is regulated by diverse environmental stimuli and physiological states. 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. The fruit fly, Drosophila melanogaster, exhibits robust recovery sleep following deprivation and represents 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 the duration and quality of recovery sleep is dependent on the 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. Both starvation and a sucrose-only diet result in increased sleep depth, suggesting that dietary protein is essential for normal sleep depth and homeostasis. Finally, we find that Drosophila insulin like peptide 2 (Dilp2) is acutely required for starvation-induced changes in sleep depth without regulating the duration of sleep. Flies lacking Dilp2 exhibit a compensatory sleep rebound following starvation-induced sleep deprivation, suggesting Dilp2 promotes resiliency 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.

Section: Plos Geneticsmentioning

confidence: 99%

Section: Plos Geneticsmentioning

confidence: 99%

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

Shah

Faville³

et al. 2020

PLoS Genet

“…While many studies have examined the interactions between sleep and feeding, these have typically compared fed and starved animals without examining the effects of specific dietary components on sleep regulation [11,36,66,67]. In Drosophila , feeding of a sugar only diet is sufficient for normal sleep duration [68], and evidence suggests that activation of sweet taste-receptors alone is sufficient to promote sleep [65,69].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous factors have been identified as essential regulators of starvation-induced sleep suppression. For example, we have found that flies mutant for the mRNA/DNA binding protein translin , the neuropeptide Leucokinin , and Astray, a regulator of serine biosynthesis, fail to suppress sleep when starved [38,66,67]. Further, activation of orexigenic Neuropeptide F -expressing neurons or the sweet-sensing Gr64f -expressing neurons suppress sleep, suggesting that activation of feeding circuits may directly inhibit sleep [69,77].…”

Section: Discussionmentioning

confidence: 99%

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

Shah

Faville³

et al. 2019

Preprint

18Sleep is a nearly universal behavior that is regulated by diverse environmental and physiological 19 stimuli. A defining feature of sleep is a homeostatic rebound following deprivation, where 20 animals compensate for lost sleep by increasing sleep duration and/or sleep depth. Fruit flies 21 exhibit robust recovery sleep following deprivation and represent a powerful model to study 22 neural circuits regulating sleep homeostasis. Numerous neuronal populations have been 23 identified in modulating sleep homeostasis as well as depth, raising the possibility that recovery 24 sleep is differentially regulated by environmental or physiological processes that induce sleep 25 deprivation. Here, we find that unlike most pharmacological and environmental manipulations 26 commonly used to restrict sleep, starvation potently induces sleep loss without a subsequent 27 rebound in sleep duration or depth. We find that both starvation and a sucrose-only diet result in 28 reduced metabolic rate and increased sleep depth, suggesting that dietary yeast protein is 29 essential for normal sleep depth and homeostasis. Finally, we find that Drosophila insulin like 30 peptide 2 (Dilp2) is required for starvation-induced changes in sleep depth without regulating the 31 duration of sleep. Remarkably, Dilp2 mutant flies require rebound sleep following sleep 32 deprivation, suggesting Dilp2 underlies resilience to sleep loss. Together, these findings reveal 33 innate resilience to starvation-induced sleep loss and identify distinct mechanisms that underlie 34 starvation-induced changes in sleep duration and depth.35 3 Author Summary 36 Sleep is nearly universal throughout the animal kingdom and homeostatic regulation represents 37 a defining feature of sleep, where animals compensate for lost sleep by increasing sleep over 38 subsequent time periods. Despite the robustness of this feature, surprisingly little is known 39 about how recovery-sleep is regulated in response to different types of sleep deprivation. Fruit 40 flies provide a powerful model for investigating the genetic regulation of sleep, and like 41 mammals, display robust recovery sleep following deprivation. Here, we find that unlike most 42 stimuli that suppress sleep, sleep deprivation by starvation does not require a homeostatic 43 rebound. These findings appear to be due to flies engaging in deeper sleep during the period of 44 partial deprivation, suggesting a natural resilience to starvation-induced sleep loss. This unique 45 resilience to starvation-induced sleep loss is dependent on Drosophila insulin-like peptide 2, 46 suggesting a critical role for insulin signaling in regulating interactions between diet and sleep 47 homeostasis. 48 4 Introduction 49Sleep is a near universal behavior that is modulated in accordance with internal and external 50 environments [1][2][3]. Numerous environmental factors can alter sleep including daily changes in 51 light and temperature, stress, social interactions, and nutrient availability [4,5]. A central factor 52 defining sleep i...

“…This phenotype occurs across diverse Drosophila melanogaster laboratory strains and outbred lines (Brown et al, 2018; Masek et al, 2014), suggesting it is not an artifact of laboratory breeding. While previous work has shown that flies fed a diet of sugar alone sleep more than starved flies (Hasegawa et al, 2017; Keene et al, 2010; Sonn et al, 2018; B. Stahl, Slocumb, Chaitin, DiAngelo, & Keene, 2017), and that high calorie diets disrupt sleep (Catterson et al, 2010; Yamazaki et al, 2012), the contributions of different dietary macronutrients to sleep regulation has not been studied systematically.…”

Section: Discussionmentioning

confidence: 99%

Dietary fatty acids promote sleep through a taste-independent mechanism

Pamboro

Keene³

2019

Preprint

300 words 16 Introduction: 559 words Abstract 19Consumption of foods that are high in fat contributes to obesity and metabolism-related 20 disorders that are increasing in prevalence and present an enormous health burden throughout 21 the world. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable 22 taste of dietary fatty acids promotes food consumption, activates reward centers in mammals, 23 and underlies hedonic feeding. Despite a central role of dietary fats in the regulation of food 24 intake and the etiology of metabolic diseases, little is known about how fat consumption 25 regulates sleep. The fruit fly, Drosophila melanogaster, provides a powerful model system for 26 the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food 27 availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented 28 fatty acids into the diet of Drosophila and measured their effects on sleep and activity. We found 29 that feeding flies a diet of hexanoic acid, a medium-chain fatty acid that is a by-product of yeast 30 fermentation, promotes sleep by increasing the number of sleep episodes. This increase in 31 sleep is dose-dependent and independent of the light-dark cues. Diets consisting of other fatty 32acids, including medium-and long-chain fatty acids, also increase sleep, suggesting many fatty 33 acid types promote sleep. To assess whether dietary fatty acids regulate sleep through the taste 34 system, we assessed sleep in flies with a mutation in the hexanoic acid receptor Ionotropic 35 receptor 56d, which is required for fatty acid taste perception. We found that these flies also 36 increase their sleep when fed a hexanoic acid diet, suggesting the sleep promoting effect of 37 hexanoic acid is not dependent on sensory perception. Overall, these results define a role for 38 fatty acids in sleep regulation, providing a foundation to investigate the molecular and neural 39 basis for fatty acid-dependent modulation of sleep duration. 40 41