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

Abstract

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.

Hormonal axes in Drosophila: regulation of hormone release and multiplicity of actions

“…The LHLKs are in turn regulated by clock neurons (Cavey et al 2016 ). IPCs and specifically DILP2, are also implicated in compensatory regulation of sleep rebound after starvation-induced sleep deprivation (Brown et al 2020 ). Furthermore, the nutrient-sensing LHLKs are part of an LK system in the brain and ventral nerve cord (totally about 24 LK neurons) that together regulate physiological processes such as diuresis, feeding, metabolism and organismal sleep activity (Yurgel et al 2019 ; Zandawala et al 2018b ).…”

Female-biased upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity

“…Future studies will also need to determine whether these sex-specific and context-dependent effects of dilp2 are observed in other phenotypes regulated by dilp2 and other dilp genes. For example, flies carrying mutations in dilp genes show changes to aging, metabolism, sleep, and immunity, among other phenotypes ( Bai et al, 2012 ; Brown et al, 2020 ; Cong et al, 2015 ; Grönke et al, 2010 ; Liu et al, 2016 ; Nässel and Vanden Broeck, 2016 ; Okamoto et al, 2009 ; Okamoto and Nishimura, 2015 ; Post et al, 2018 ; Post et al, 2019 ; Slaidina et al, 2009 ; Stafford et al, 2012 ; Zhang et al, 2009 ; Brogiolo et al, 2001 ; Cognigni et al, 2011 ; Linneweber et al, 2014 ; Semaniuk et al, 2018 ; Suzawa et al, 2019 ; Ugrankar et al, 2018 ). Further, it will be interesting to determine whether the sex-specific regulation of sun is observed in any other contexts, and whether it will influence sex differences in phenotypes associated with altered IIS activity, such as life span.…”

Modulation of sleep-courtship balance by nutritional status in Drosophila

“…Previous studies have identified several neuronal populations that mediate the effects of dietary protein and amino acids on adult Drosophila behavior. These include dopaminergic Wedge neurons, EB Ring5 neurons, and peptidergic neurons expressing diuretic hormone-44, insulin-like peptide-2, or leucokinin ( Brown et al, 2020 ; Ki and Lim, 2019 ; Liu et al, 2017 ; Murphy et al, 2016 ; Yang et al, 2018 ; Yurgel et al, 2019 ). It would be interesting to determine whether these neurons are involved in modulating the sleep-courtship balance by nutrition.…”