A single pair of leucokinin neurons are modulated by feeding state and regulate sleep–metabolism interactions

Yurgel, Maria E.; Kakad, Priyanka; Zandawala, Meet; Nässel, Dick R.; Godenschwege, Tanja A.; Keene, Alex C.

doi:10.1371/journal.pbio.2006409

Cited by 87 publications

(145 citation statements)

References 92 publications

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“…Central nervous system neurons control sleep in a top-down fashion [85, 86], but bottom-up metabolic signals from glia [17, 24, 87, 88], muscle cells [32, 88-90] and adipocytes [91, 92] affect activity of sleep regulating neurons. While several gene products have been reported to regulate both metabolism and sleep [4, 9, 21-23, 25, 26, 32, 41, 89, 90, 93, 94], the mechanism of the metabolic regulation of sleep has heretofore remained opaque.…”

Section: Discussionmentioning

confidence: 99%

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

Grubbs

Lopes

Linden

et al. 2019

Preprint

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ABSTRACTMany lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During C. elegans sleep, energetic stores are allocated to non-neural tasks with a resultant drop in the overall fat stores and energy charge. Mutants lacking KIN-29, the C. elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have low ATP levels despite high fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores corrects adiposity and sleep defects of kin-29 mutants. kin-29 sleep and energy homeostasis roles map to a small number of sensory neurons that act upstream of fat regulation as well as of central sleep-controlling neurons, suggesting hierarchical somatic/neural interactions regulating sleep and energy homeostasis. Genetic interaction between kin-29 and the histone deacetylase hda-4 coupled with subcellular localization studies indicate that KIN-29 acts in the nucleus to regulate sleep. We propose that KIN-29/SIK acts in nuclei of sensory neuroendocrine cells to transduce low cellular energy charge into the mobilization of energy stores, which in turn promotes sleep.HighlightsSleep is associated with fat mobilization and low ATP levelsMetabolic regulation of sleep requires the salt-induced kinase (SIK) homolog KIN-29KIN-29 acts in sensory neurons upstream of sleep-promoting neuronsNuclear localization of KIN-29 is required for the metabolic regulation of sleepA type 2 histone deacetylase acts down stream of KIN-29 in the regulation of sleep.Liberation of energy from fat-storage cells promotes sleep.Beta-oxidation promotes sleep.

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Section: Discussionmentioning

confidence: 99%

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

Grubbs

Lopes

Linden

et al. 2019

Preprint

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“…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%

“…A central question is how neural circuits that mediate starvation-induced sleep suppression interface with the IPCs that regulate sleep depth during the starvation period. We have found that Leucokinin neurons in the lateral horn signal to IPC neurons that express the Leucokinin Receptor to suppress sleep during starvation [67]. These findings raise the possibility of a connection between LkR signaling in the IPCs and Dilp2 function, that in turn increase sleep depth during periods of starvation.…”

Section: Discussionmentioning

confidence: 99%

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

Brown

Shah

Faville³

et al. 2019

Preprint

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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...

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“…Knockdown of Lkr in IPCs results in altered dilp transcription in a diet‐specific manner, suggesting that leucokinin interacts with insulin signaling to control metabolism and stress response. In addition, starvation‐induced sleep in flies is also under the control of leucokinin neurons‐IPC connectivity (Yurgel et al, ). Finally, the neuropeptide Allatostatin A (AstA) positively regulates expression of dilp3 in IPCs (Hentze et al, ).…”

Section: Factors Regulating Ipcs and Dilp Productionmentioning

confidence: 99%

Regulation of insulin and adipokinetic hormone/glucagon production in flies

Ahmad

Perrimon

2019

WIREs Developmental Biology

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Metabolic homeostasis is under strict regulation of humoral factors across various taxa. In particular, insulin and glucagon, referred to in Drosophila as Drosophila insulin‐like peptides (DILPs) and adipokinetic hormone (AKH), respectively, are key hormones that regulate metabolism in most metazoa. While much is known about the regulation of DILPs, the mechanisms regulating AKH/glucagon production is still poorly understood. In this review, we describe the various factors that regulate the production of DILPs and AKH and emphasize the need for future studies to decipher how energy homeostasis is governed in Drosophila. This article is categorized under: Invertebrate Organogenesis > Flies Signaling Pathways > Global Signaling Mechanisms

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A single pair of leucokinin neurons are modulated by feeding state and regulate sleep–metabolism interactions

Cited by 87 publications

References 92 publications

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

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

Regulation of insulin and adipokinetic hormone/glucagon production in flies

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