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


Autoři: Elizabeth B. Brown aff001;  Kreesha D. Shah aff001;  Richard Faville aff003;  Benjamin Kottler aff003;  Alex C. Keene aff001
Působiště autorů: Department of Biological Sciences, Florida Atlantic University, Jupiter, Florida, United States of America aff001;  Wilkes Honors College, Florida Atlantic University, Jupiter, Florida, United States of America aff002;  Burczyk/Faville/Kottler LTD, London, England aff003
Vyšlo v časopise: Drosophila insulin-like peptide 2 mediates dietary regulation of sleep intensity. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008270
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008270

Souhrn

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.

Klíčová slova:

Analysis of variance – Diet – Drosophila melanogaster – Homeostasis – Neurons – Sleep – Sleep deprivation – Starvation


Zdroje

1. Keene AC, Duboue ER. The origins and evolution of sleep. J Exp Biol. 2018;12: jeb159533. doi: 10.1242/jeb.159533

2. Joiner WJ. Unraveling the evolutionary determinants of sleep. Curr Biol. 2016;26: R1073–R1087. doi: 10.1016/j.cub.2016.08.068 27780049

3. Allada R, Siegel JM. Unearthing the phylogenetic roots of sleep. Curr Biol. 2008;18: R670–R679. doi: 10.1016/j.cub.2008.06.033 18682212

4. Donlea JM. Neuronal and molecular mechanisms of sleep homeostasis. Curr Opin Insect Sci. 2017;24: 51–57. doi: 10.1016/j.cois.2017.09.008 29208223

5. Tougeron K, Abram PK. An ecological perspective on sleep disruption. Am Nat. 2017;190: E55–E66. doi: 10.1086/692604 28829644

6. Campbell SS, Tobler I. Animal sleep: a review of sleep duration across phylogeny. Neurosci Biobehav Rev. 1984;8: 269–300. doi: 10.1016/0149-7634(84)90054-x 6504414

7. Hartmann E. The function of sleep. Annu Psychoanal. 1974;2: 271–289.

8. Liu S, Liu Q, Tabuchi M, Wu M. Sleep drive Is encoded by neural plastic changes in a dedicated circuit. Cell. 2016;165: 1347–1360. doi: 10.1016/j.cell.2016.04.013 27212237

9. Seidner G, Robinson JE, Wu M, Worden K, Masek P, Roberts SW, Keene AC, Joiner WJ. Identification of neurons with a privileged role in sleep homeostasis in Drosophila melanogaster. Curr Biol. 2015;25: 2928–2938. doi: 10.1016/j.cub.2015.10.006 26526372

10. Danguir J, Nicolaidis S. Dependence of sleep on nutrients' availability. Physiol Behav. 1979;22: 735–740. doi: 10.1016/0031-9384(79)90240-3 225752

11. Keene AC, Duboué ER, McDonald DM, Dus M, Suh GS, Waddell S, Blau J. Clock and cycle limit starvation-induced sleep loss in Drosophila. Curr Biol. 2010;20: 1209–1215. doi: 10.1016/j.cub.2010.05.029 20541409

12. Griffith LC. Neuromodulatory control of sleep in Drosophila melanogaster: Integration of competing and complementary behaviors. Curr Opin Neurobiol. 2013;23: 819–823. doi: 10.1016/j.conb.2013.05.003 23743247

13. Yurgel ME, Masek P, DiAngelo J, Keene AC. Genetic dissection of sleep-metabolism interactions in the fruit fly. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2014;201: 869–77. doi: 10.1007/s00359-014-0936-9 25236355

14. Crocker A, Shahidullah M, Levitan IB, Sehgal A. Identification of a neural circuit that underlies the effects of octopamine on sleep:wake behavior. Neuron. 2010;65: 670–681. doi: 10.1016/j.neuron.2010.01.032 20223202

15. Kréneisz O, Chen X, Fridell YW, Mulkey DK. Glucose increases activity and Ca2+ in insulin-producing cells of adult Drosophila. Neuroreport. 2010;21: 1116–1120. doi: 10.1097/WNR.0b013e3283409200 20890228

16. Varin C, Rancillac A, Geoffroy H, Arthaud S, Fort P, Gallopin T. Glucose induces slow-wave sleep by exciting the sleep-promoting neurons in the ventrolateral preoptic nucleus: a new link between sleep and metabolism. J Neurosci. 2015;35: 9900–9911. doi: 10.1523/JNEUROSCI.0609-15.2015 26156991

17. Chakravarti L, Moscato EH, Kayser MS. Unraveling the neurobiology of sleep and sleep disorders using Drosophila. 2017;121: 253–285. doi: 10.1016/bs.ctdb.2016.07.010

18. Artiushin G, Sehgal A. The Drosophila circuitry of sleep–wake regulation. Curr Opin Neurobiol. 2017;44: 243–250. doi: 10.1016/j.conb.2017.03.004 28366532

19. Donlea JM, Pimentel D, Talbot CB, Kempf A, Omoto JJ, Hartenstein V, Miesenböck G. Recurrent circuitry for balancing sleep need and sleep. Neuron. 2018;97: 378–389.e4. doi: 10.1016/j.neuron.2017.12.016

20. Pimentel D, Donlea JM, Talbot CB, Song SM, Thurston AJF, Miesenböck G. Operation of a homeostatic sleep switch. Nature. 2016;536: 333–337. doi: 10.1038/nature19055 27487216

21. Toda H, Williams JA, Gulledge M, Sehgal A. A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science. 2019;363: 509–515. doi: 10.1126/science.aat1650 30705188

22. Thimgan MS, Suzuki Y, Seugnet L, Gottschalk L, Shaw PJ. The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss. 2010;8: e1000466. doi: 10.1371/journal.pbio.1000466

23. Donlea J, Leahy A, Thimgan MS, Suzuki Y, Hughson BN, Sokolowski MB, Shaw PJ. Foraging alters resilience/vulnerability to sleep disruption and starvation in Drosophila. Proc Natl Acad Sci USA. 2012;109: 2613–2618. doi: 10.1073/pnas.1112623109 22308351

24. van Alphen B, Yap MH, Kirszenblat L, Kottler B, van Swinderen B. A dynamic deep sleep stage in Drosophila. J Neurosci. 2013;33: 6917–6927. doi: 10.1523/JNEUROSCI.0061-13.2013 23595750

25. Faville R, Kottler B, Goodhill GJ, Shaw PJ, van Swinderen B. How deeply does your mutant sleep? Probing arousal to better understand sleep defects in Drosophila. Sci Rep. 2015;13: 8454. doi: 10.1038/srep08454

26. Yap MHW, Grabowska MJ, Rohrscheib C, Jeans R, Troup M, Paulk AC, van Alphen B, Shaw PJ, van Swinderen B. Oscillatory brain activity in spontaneous and induced sleep stages in flies. Nat Commun. 2017;8: 1815. doi: 10.1038/s41467-017-02024-y 29180766

27. Pfeiffenberger C, Lear BC, Keegan KP, Allada R. Locomotor activity level monitoring using the Drosophila activity monitoring (DAM) system. Cold Spring Harb Protoc. 2010;2010: pdb.prot5518. doi: 10.1101/pdb.prot5518

28. Stahl BA, Slocumb ME, Chaitin H, DiAngelo JR, Keene AC. Sleep-dependent modulation of metabolic rate in Drosophila. Sleep. 2017;40: zsx084. doi: 10.1093/sleep/zsx084

29. Harshman LG, Hoffmann AA, Clark AG. Selection for starvation resistance in Drosophila melanogaster: Physiological correlates, enzyme activities and multiple stress responses. J Evol Biol. 1999;12: 370–379. doi: 10.1046/j.1420-9101.1999.00024.x

30. Andretic R, Shaw PJ. Essentials of sleep recordings in Drosophila: Moving beyond sleep time. Methods Enzymol. 2005;393: 759–772. doi: 10.1016/S0076-6879(05)93040-1 15817323

31. Brown EB, Torres J, Bennick RA, Rozzo V, Kerbs A, DiAngelo JR, Keene AC. Variation in sleep and metabolic function is associated with latitude and average temperature in Drosophila melanogaster. Ecol Evol. 2018;8: 4084–4097. doi: 10.1002/ece3.3963 29721282

32. Khericha M, Kolenchery JB, Tauber E. Neural and non-neural contributions to sexual dimorphism of mid-day sleep in Drosophila melanogaster: a pilot study. Physiol Entomol. 2016;41: 327–334. doi: 10.1111/phen.12134 27840547

33. Lindsley DL, Grell EH. Genetic Variations of Drosophila melanogaster. Publs Carnegie Instn. 1968; 627: 469pp.

34. Kempf A, Song SM, Talbot CB, Miesenböck G. A potassium channel β-subunit couples mitochondrial electron transport to sleep. Nature. 2019;568: 230–234. doi: 10.1038/s41586-019-1034-5 30894743

35. de Camargo R, Phaff HJ. Yeasts occurring in Drosophila flies and in fermenting tomato fruits in northern California. J Food Sci. 1957;22: 367–372. doi: 10.1111/j.1365-2621.1957.tb17024.x

36. Phaff HJ, Miller MW, Recca JA, Shifrine M, Mrak EM. Yeasts found in the alimentary canal of Drosophila. Ecology. 1956;37: 533–538. doi: 10.2307/1930176

37. Liu Q, Tabuchi M, Liu S, Kodama L, Horiuchi W, Daniels J, Chiu L, Baldoni D, Wu MN. Branch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger. Science. 2017;356: 534–539. doi: 10.1126/science.aal3245 28473588

38. Dus M, Min S, Keene AC, Lee GY, Suh GSB. Taste-independent detection of the caloric content of sugar in Drosophila. Proc Natl Acad Sci USA. 2011;108: 11644–11649. doi: 10.1073/pnas.1017096108 21709242

39. Murakami K, Yurgel ME, Stahl BA, Masek P, Mehta A, Heidker R, Bollinger W, Gingras RM, Kim YJ, Ja WW, Suter B, DiAngelo JR, Keene AC. Translin is required for metabolic regulation of sleep. Curr Biol. 2016;26: 972–980. doi: 10.1016/j.cub.2016.02.013 27020744

40. DiAngelo JR, Erion R, Crocker A, Sehgal A. The central clock neurons regulate lipid storage in Drosophila. PLoS One. 2011;6: e19921. doi: 10.1371/journal.pone.0019921 21625640

41. Rajan A, Perrimon N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell. 2012;151: 123–137. doi: 10.1016/j.cell.2012.08.019 23021220

42. Ikeya T, Galic M, Belawat P, Nairz K, Hafen E. Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Curr Biol. 2002;12: 1293–1300. doi: 10.1016/s0960-9822(02)01043-6 12176357

43. Birse RT, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, Ocorr K, Bodmer R, Oldham S. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab. 2010;12: 533–544. doi: 10.1016/j.cmet.2010.09.014 21035763

44. Metaxakis A, Tain L, Grönke, Hendrich O, Hinze Y, Birras U, Partridge L. Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila. PLoS Biol. 2014;12: e1001824. doi: 10.1371/journal.pbio.1001824 24690889

45. Cong X, Wang H, Liu Z, He C, An C, Zhao Z. Regulation of sleep by insulin-like peptide system in Drosophila melanogaster. Sleep. 2015;38: 1075–1083. doi: 10.5665/sleep.4816 25581915

46. Grönke S, Clarke DF, Broughton S, Andrews TD, Partridge L. Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 2010;6: e1000857. doi: 10.1371/journal.pgen.1000857 20195512

47. Karpac J, Hull-Thompson J, Falleur M, Jasper H. JNK signaling in insulin-producing cells is required for adaptive responses to stress in Drosophila. Aging Cell. 2009;8: 288–295. doi: 10.1111/j.1474-9726.2009.00476.x 19627268

48. Nath RD, Bedbrook CN, Abrams MJ, Basinger T, Bois JS, Prober DA, Sternberg PW, Gradinaru V, Goentoro L. The jellyfish Cassiopea exhibits a sleep-like state. Curr Biol. 2017;27: 2984-2990.e3. doi: 10.1016/j.cub.2017.08.014

49. Krashes MJ, DasGupta S, Vreede A, White B, Armstrong JD, Waddell S. A neural circuit mechanism integrating motivational state with memory expression in Drosophila. Cell. 2009;139: 416–27. doi: 10.1016/j.cell.2009.08.035 19837040

50. Krashes MJ, Waddell S. Rapid consolidation to a radish and protein synthesis-dependent long-term memory after single-session appetitive olfactory conditioning in Drosophila. J Neurosci. 2008;19: 3103–3113. doi: 10.1523/JNEUROSCI.5333-07.2008

51. Cervantes-Sandoval I, Davis RL. Distinct traces for appetitive versus aversive olfactory memories in DPM neurons of Drosophila. Curr Biol. 2012;22: 1247–1252. doi: 10.1016/j.cub.2012.05.009 22658595

52. Borbély AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1: 195–204. doi: 10.1111/jsr.12371 7185792

53. Donlea JM, Pimentel D, Miesenböck G. Neuronal machinery of sleep homeostasis in Drosophila. Neuron. 2014;81: 860–872. doi: 10.1016/j.neuron.2013.12.013 24559676

54. Goodwin PR, Meng A, Moore J, Hobin M, Fulga TA, Van Vactor D, Griffith LC. MicroRNAs regulate sleep and sleep homeostasis in Drosophila. Cell Rep. 2018;23: 3776–3786. doi: 10.1016/j.celrep.2018.05.078 29949763

55. Vanderheyden WM, Goodman AG, Taylor RH, Frank MG, Van Dongen HPA, Gerstner JR. Astrocyte expression of the Drosophila TNF-alpha homologue, Eiger, regulates sleep in flies. PLOS Genet. 2018;14: e1007724. doi: 10.1371/journal.pgen.1007724 30379810

56. Allada R, Cirelli C, Sehgal A. Molecular mechanisms of sleep homeostasis in flies and mammals. Cold Spring Harb Perspect Biol. 2017;9: a027730. doi: 10.1101/cshperspect.a027730 28432135

57. Liu G, Seiler H, Wen A, Zars T, Ito K, Wolf R, Heisenberg M, Liu L. Distinct memory traces for two visual features in the Drosophila brain. Nature. 2006;439: 551–556. doi: 10.1038/nature04381 16452971

58. Pan Y, Zhou Y, Guo C, Gong H, Gong Z, Liu L. Differential roles of the fan-shaped body and the ellipsoid body in Drosophila visual pattern memory. 2009;16: 289–295. doi: 10.1101/lm.1331809.16

59. Sitaraman D, Aso Y, Jin X, Chen N, Felix M, Rubin GM, Nitabach MN. Propagation of homeostatic sleep signals by segregated synaptic microcircuits of the Drosophila mushroom body. Curr Biol. 2015;25: 2517–2527. doi: 10.1016/j.cub.2015.09.017

60. Tabuchi M, Lone SR, Liu Q, Liu Q, Zhang J, Spira AP, Wu MN. Sleep interacts with aβ to modulate intrinsic neuronal excitability. Curr Biol. 2015;25: 702–712. doi: 10.1016/j.cub.2015.01.016 25754641

61. Shaw PJ, Cirelli C, Greenspan RJ, Tononi G. Correlates of sleep and waking in Drosophila melanogaster. Science. 2000;287: 1834–1837. doi: 10.1126/science.287.5459.1834 10710313

62. Ho KS, Sehgal A. Drosophila melanogaster: An insect model for fundamental studies of sleep. Methods Enzymol. 2005;393: 772–793. doi: 10.1016/S0076-6879(05)93041-3 15817324

63. Harbison ST, Mackay TF, Anholt RR. Understanding the neurogenetics of sleep: progress from Drosophila. Trends Genet. 2009;25: 262–269. doi: 10.1016/j.tig.2009.04.003 19446357

64. Beckwith EJ, Geissmann Q, French AS, Gilestro GF. Regulation of sleep homeostasis by sexual arousal. Elife. 2017;6: e27445. doi: 10.7554/eLife.27445 28893376

65. Machado DR, Afonso DJ, Kenny AR, Öztürk-Çolak A, Moscato EH, Mainwaring B, Kayser M, Koh K. Identification of octopaminergic neurons that modulate sleep suppression by male sex drive. Elife. 2017;6: e23130. doi: 10.7554/eLife.23130 28510528

66. Szymusiak R. Hypothalamic versus neocortical control of sleep. Curr Opin Pulm Med. 2010;16: 530–535. doi: 10.1097/MCP.0b013e32833eec92 20739890

67. Hanlon EC, Vyazovskiy VV, Faraguna U, Tononi G, Cirelli C. Synaptic potentiation and sleep need: clues from molecular and electrophysiological studies. Curr Top Med Chem. 2011;11: 2472–2482. doi: 10.2174/156802611797470312 21906017

68. Hasegawa T, Tomita J, Hashimoto R, Ueno T, Kume S, Kume K. Sweetness induces sleep through gustatory signalling independent of nutritional value in a starved fruit fly. Sci Rep. 2017;7: 14355. doi: 10.1038/s41598-017-14608-1 29084998

69. Sonn JY, Lee J, Sung MK, Ri H, Choi JK, Lim C, Choe J. Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster. Proc Natl Acad Sci USA. 2018;115: 7129–7134. doi: 10.1073/pnas.1719033115 29915051

70. Yurgel ME, Kakad P, Zandawala M, Nässel DR, Godenschwege TA, Keene AC. A single pair of leucokinin neurons are modulated by feeding state and regulate sleep–metabolism interactions. PLoS Biol. 2019;17: e2006409. doi: 10.1371/journal.pbio.2006409 30759083

71. Linford NJ, Chan TP, Pletcher SD. Re-patterning sleep architecture in Drosophila through gustatory perception and nutritional quality. PLoS Genet. 2012;8: e1002668. doi: 10.1371/journal.pgen.1002668 22570630

72. Linford NJ, Ro J, Chung BY, Pletcher SD. Gustatory and metabolic perception of nutrient stress in Drosophila. Proc Natl Acad Sci USA. 2015;112: 2587–2592. doi: 10.1073/pnas.1401501112 25675472

73. Broughton SJ, Slack C, Alic N, Metaxakis A, Bass TM, Driege Y, Partridge L. DILP-producing median neurosecretory cells in the Drosophila brain mediate the response of lifespan to nutrition. Aging Cell. 2010;9: 336–346. doi: 10.1111/j.1474-9726.2010.00558.x 20156206

74. Fosque BF, Sun Y, Dana H, Yang CT, Ohyama T, Tadross MR, Patel R, Zlatic M, Kim DS, Ahrens MB, Jayaraman V, Looger LL, Schreiter ER. Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators. Science. 2015;347: 755–760. doi: 10.1126/science.1260922 25678659

75. Gao XJ, Riabinina O, Li J, Potter CJ, Clandinin TR, Luo L. A transcriptional reporter of intracellular Ca(2+) in Drosophila. Nat Neurosci. 2015;18: 917–925. doi: 10.1038/nn.4016 25961791

76. Rulifson EJ, Kim SK, Nusse R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science. 2002;296: 1118–1120. doi: 10.1126/science.1070058 12004130

77. Broughton S, Alic N, Slack C, Bass T, Ikeya T, Vinti G, Tommasi AM, Driege Y, Hafen E, Partridge L. Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs. PLoS One. 2008;3: e3721. doi: 10.1371/journal.pone.0003721 19005568

78. Post S, Karashchuk G, Wade JD, Sajid W, De Meyts P, Tatar M. Drosophila insulin-like peptides DILP2 and DILP5 differentially stimulate cell signaling and glycogen phosphorylase to regulate longevity. Front Endocrinol (Lausanne). 2018;9: 245. doi: 10.3389/fendo.2018.00245

79. Birse RT, Soderberg JA, Luo J, Winther AM, Nässel DR. Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR. J Exp Biol. 2011;214: 4201–4208. doi: 10.1242/jeb.062091 22116763

80. Sudhakar SR, Varghese J. Insulin signalling activates multiple feedback loops to elicit hunger-induced feeding in Drosophila bioRxiv. 2018. doi: 10.1101/364554

81. Chung BY, Ro J, Hutter SA, Miller KM, Guduguntla LS, Kondo S, Pletcher SD. Drosophila neuropeptide F signaling independently regulates feeding and sleep-wake behavior. Cell Rep. 2017;19: 2441–2450. doi: 10.1016/j.celrep.2017.05.085 28636933

82. Ni JQ, Markstein M, Binari R, Pfeiffer B, Liu LP, Villalta C, Booker M, Perkins L, Perrimon N. Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nat Methods. 2008;5: 49–51. doi: 10.1038/nmeth1146 18084299

83. Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, Sehgal A, Pack AI. Rest in Drosophila is a sleep-like state. Neuron. 2000;25: 129–138. doi: 10.1016/s0896-6273(00)80877-6 10707978

84. Kubrak OI, Lushchak OV, Zandawala M, Nässel DR. Systemic corazonin signalling modulates stress responses and metabolism in Drosophila. Open Biol. 2016;6: 160152. doi: 10.1098/rsob.160152 27810969


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