Research Overview on Corpora Cardiaca Function of Drosophila melanogaster

doi:10.12300/j.issn.1674-5817.2025.106

Abstract

Abstract:

Taking the corpora cardiaca (CC) of Drosophila melanogaster as the central focus, this review establishes a four-dimensional framework of "development-secretion-regulation-function" to systematically summarize the core role of CC in glucose metabolic homeostasis. Drosophila has a mature genetic toolkit and high gene homology with humans, making it an ideal model for studying energy balance. CC and insulin-producing cells (IPCs) correspond to vertebrate pancreatic α/β cells respectively, jointly regulating hemolymph glucose and trehalose concentrations through adipokinetic hormone (AKH) and Drosophila insulin-like peptides (DILPs). This review first discusses developmental process of CC: it originates from head mesoderm, undergoes embryonic specification, larval expansion, pupal remodeling, and adult fusion, ultimately forming a bilobed organ surrounding the esophagus. Genes and signaling pathways such as sine oculis, glass, Notch, dpp, and hh control this process in a strict spatiotemporal pattern, and a mutation at any node can cause CC absence or functional defects. CC can receive external regulation, integrating multiple inputs including nutrients and brain-gut secretory factors. During starvation, cell-surface glucose sensors directly sense hypoglycaemia and increase AKH secretion. Enteroendocrine cells exert positive/negative feedback on CC through peptides such as allatostatin A (AstA), bursicon α, and neuropeptide F (NPF). Brain dopamine (DA), pigment-dispersing factor (PDF), and DILP1/2 form neuroendocrine antagonism to precisely regulate AKH release. The CC mainly secretes three types of molecules: AKH mobilizes glycogen and triacylglycerol in the fat body via the adipokinetic hormone receptor (AKHR)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. Limostatin (Lst) inhibits DILP secretion from IPCs via its receptor. Insulin antagonist protein 2 (imaginal morphogenesis protein-late 2, ImpL2) antagonizes DILPs and inhibits the target of rapamycin (TOR) pathway, thereby coupling nutritional status with developmental process. The AKH/AKHR axis drives sugar/lipid mobilization and foraging hyperactivity under starvation, high-fat, or heat stress. Prothoracicotropic hormone (PTTH) and ImpL2 mediate CC–prothoracic gland axis to ensure timely ecdysone release after the critical weight. CC axons innervate the crop, regulating emptying rate. AKH-forkhead box O (FoxO)-small ventral lateral neurons (s-LNv) circuit inhibits starvation-induced sleep loss, maintaining circadian homeostasis. This review summarizes the developmental mechanisms of CC, action mechanisms of secreted hormones, and interactions with other tissues, which not only helps scholars understand regulatory mechanisms of insect energy homeostasis, but also provides novel perspectives and targets for research on metabolic disorders and related diseases in invertebrates.

Key words: Drosophila melanogaster, Metabolism, Corpora cardiaca, Adipokinetic hormone, Regulation

CLC Number:

Q95-33

WANG Hanyue,CHEN Jiawei,GAO Xiangbin,et al. Research Overview on Corpora Cardiaca Function of Drosophila melanogaster[J]. Laboratory Animal and Comparative Medicine, 2025, 45(6): 705-718. DOI: 10.12300/j.issn.1674-5817.2025.106.

Figures/Tables 3

Figure 1 Development process of corpora cardiaca in Drosophila melanogaster during embryonic and pupal stagesNote： CC， corpus cardiacum； CA， corpus allatum； RG， ring gland； AO， aorta； Br， brain； Es， esophagus； Pr， proventriculus； Vg， ventral ganglion.

Figure 2 Regulation of corpora cardiaca by other organs in Drosophila melanogaster larvae and adultsNote： Larva CC， larva corpora cardiaca； MNC， median neurosecretory cells； IPCs， insulin-producing cells； AbdG， abdominal ganglia； DANs， dopaminergic neurons； EECs A，M，anterior and middle midgut enteroendocrine cells； EECs P， posterior midgut enteroendocrine cells； Adult CC， adult corpora cardiaca； DILP2， Insulin-like peptide 2； PDF， pigment-dispersing factor； DA， dopamine； NPF， neuropeptide F； AstA， allatostatin A； Bursicon α， Bursicon α. "→"， promotion of adipokinetic hormone （AKH） release； "⊥"， pointing to the larval and adult corpora cardiaca denotes inhibition of AKH release， whereas the one directed at DILP1 represents negative regulation of DILP1.

Figure 3 Corpora cardiaca regulate physiological processes of target organs via hormone secretionNote： AKHR， adipokinetic hormone receptor； cAMP， cyclic adenosine monophosphate； PKA， protein kinase A； IPCs， insulin-producing cells； LSTR， limostatin receptor； PG， prothoracic gland； InR， insulin receptor； s-LNv， small ventral lateral neurons； AKH，adipokinetic hormone； DILP2， Drosophila insulin-like peptide 2； LST， limostatin； "→"， activation of the receptor on the target organ.

References 106

[1]	VAN DYCK H. Book review: insect physiological ecology. mechanisms and patterns[J]. J Insect Conserv, 2005, 9(3):225-226. DOI:10.1007/s10841-005-5474-x .
[2]	DROUJININE I A, PERRIMON N. Interorgan communication pathways in physiology: focus on Drosophila [J]. Annu Rev Genet, 2016, 50:539-570. DOI:10.1146/annurev-genet-121415-122024 .
[3]	IKEYA T, GALIC M, BELAWAT P, et al. Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila [J]. Curr Biol, 2002, 12(15):1293-1300. DOI:10.1016/s0960-9822(02)01043-6 .
[4]	KIM S K, RULIFSON E J. Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells[J]. Nature, 2004, 431(7006):316-320. DOI:10.1038/nature02897 .
[5]	BROGIOLO W, STOCKER H, IKEYA T, et al. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control[J]. Curr Biol, 2001, 11(4):213-221. DOI:10.1016/s0960-9822(01)00068-9 .
[6]	CALDERON D, BLECHER-GONEN R, HUANG X F, et al. The continuum of Drosophila embryonic development at single-cell resolution[J]. Science, 2022, 377(6606):eabn5800. DOI:10.1126/science.abn5800 .
[7]	LU T C, BRBIĆ M, PARK Y J, et al. Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution[J]. Science, 2023, 380(6650):eadg0934. DOI:10.1126/science.adg0934 .
[8]	WINDING M, PEDIGO B D, BARNES C L, et al. The connectome of an insect brain[J]. Science, 2023, 379(6636):eadd9330. DOI:10.1126/science.add9330 .
[9]	ÖZEL M N, GIBBS C S, HOLGUERA I, et al. Coordinated control of neuronal differentiation and wiring by sustained transcription factors[J]. Science, 2022, 378(6626):eadd1884. DOI:10.1126/science.add1884 .
[10]	AGI E, REIFENSTEIN E T, WIT C, et al. Axonal self-sorting without target guidance in Drosophila visual map formation[J]. Science, 2024, 383(6687):1084-1092. DOI:10.1126/science.adk3043 .
[11]	WEAVER K J, HOLT R A, HENRY E, et al. Effects of hunger on neuronal histone modifications slow aging in Drosophila [J]. Science, 2023, 380(6645):625-632. DOI:10.1126/science.ade1662 .
[12]	FURUSAWA K, ISHII K, TSUJI M, et al. Presynaptic Ube3a E3 ligase promotes synapse elimination through down-regulation of BMP signaling[J]. Science, 2023, 381(6663):1197-1205. DOI:10.1126/science.ade8978 .
[13]	HANSON M A, GROLLMUS L, LEMAITRE B. Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila [J]. Science, 2023, 381(6655):eadg5725. DOI:10.1126/science.adg5725 .
[14]	GUTIÉRREZ-GARCÍA K, AUMILLER K, DODGE R, et al. A conserved bacterial genetic basis for commensal-host specificity[J]. Science, 2024, 386(6726):1117-1122. DOI:10.1126/science.adp7748 .
[15]	GUO P F, LI B, DONG W, et al. PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation[J]. Science, 2024, 385(6709):eadf4478. DOI:10.1126/science.adf4478 .
[16]	KOWALCZYK W, ROMANELLI L, ATKINS M, et al. Hippo signaling instructs ectopic but not normal organ growth[J]. Science, 2022, 378(6621):eabg3679. DOI:10.1126/science.abg3679 .
[17]	JACOBS J, PAGANI M, WENZL C, et al. Widespread regulatory specificities between transcriptional co-repressors and enhancers in Drosophila [J]. Science, 2023, 381(6654):198-204. DOI:10.1126/science.adf6149 .
[18]	GANDARA L, JACOBY R, LAURENT F, et al. Pervasive sublethal effects of agrochemicals on insects at environmentally relevant concentrations[J]. Science, 2024, 386(6720):446-453. DOI:10.1126/science.ado0251 .
[19]	FINNEGAN D J. Drosophila: A laboratory handbook[J]. Trends Biotechnol, 1990, 8:298.
[20]	PARK S, BUSTAMANTE E L, ANTONOVA J, et al. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling[J]. PLoS Genet, 2011, 7(8):e1002241. DOI:10.1371/journal.pgen.1002241 .
[21]	GARCÍA-FERRÉS M, SÁNCHEZ-HIGUERAS C, ESPINOSA-VÁZQUEZ J M, et al. Specification of the endocrine primordia controlling insect moulting and metamorphosis by the JAK/STAT signalling pathway[J]. PLoS Genet, 2022, 18(10):e1010427. DOI:10.1371/journal.pgen.1010427 .
[22]	LEE G, PARK J H. Hemolymph sugar homeostasis and starvation-induced hyperactivity affected by genetic manipulations of the adipokinetic hormone-encoding gene in Drosophila melanogaster [J]. Genetics, 2004, 167(1):311-323. DOI:10.1534/genetics.167.1.311 .
[23]	DAI J D, GILBERT L I. Metamorphosis of the corpus allatum and degeneration of the prothoracic glands during the larval-pupal-adult transformation of Drosophila melanogaster: a cytophysiological analysis of the ring gland[J]. Dev Biol, 1991, 144(2):309-326. DOI:10.1016/0012-1606(91)90424-2 .
[24]	BODENSTEIN D. The postembryonic development of Drosophila [J]. Biol. Drosophila, 1950. DOI:http://dx.doi.org/ .
[25]	RULIFSON E J, KIM S K, NUSSE R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes[J]. Science, 2002, 296(5570):1118-1120. DOI:10.1126/science.1070058 .
[26]	CHEYETTE B N, GREEN P J, MARTIN K, et al. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system[J]. Neuron, 1994, 12(5):977-996. DOI:10.1016/0896-6273(94)90308-5 .
[27]	CAPOVILLA M, ELDON E D, PIRROTTA V. The giant gene of Drosophila encodes a b-ZIP DNA-binding protein that regulates the expression of other segmentation gap genes[J]. Development, 1992, 114(1):99-112. DOI:10.1242/dev.114.1.99 .
[28]	MOHLER J, ELDON E D, PIRROTTA V. A novel spatial transcription pattern associated with the segmentation gene, giant, of Drosophila [J]. EMBO J, 1989, 8(5):1539-1548. DOI:10.1002/j.1460-2075.1989.tb03538.x .
[29]	ALBERGA A, BOULAY J L, KEMPE E, et al. The snail gene required for mesoderm formation in Drosophila is expressed dynamically in derivatives of all three germ layers[J]. Development, 1991, 111(4):983-992. DOI:10.1242/dev.111.4.983 .
[30]	BOULAY J L, DENNEFELD C, ALBERGA A. The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers[J]. Nature, 1987, 330(6146):395-398. DOI:10.1038/330395a0 .
[31]	BODMER R. The gene tinman is required for specification of the heart and visceral muscles in Drosophila [J]. Development, 1993, 118(3):719-729. DOI:10.1242/dev.118.3.719 .
[32]	DE VELASCO B, SHEN J, GO S, et al. Embryonic development of the Drosophila corpus cardiacum, a neuroendocrine gland with similarity to the vertebrate pituitary, is controlled by sine oculis and glass [J]. Dev Biol, 2004, 274(2):280-294. DOI:10.1016/j.ydbio.2004.07.015 .
[33]	WHARTON K A, RAY R P, GELBART W M. An activity gradient of decapentaplegic is necessary for the specification of dorsal pattern elements in the Drosophila embryo[J]. Development, 1993, 117(2):807-822. DOI:10.1242/dev.117.2.807 .
[34]	HOLLEY S A, JACKSON P D, SASAI Y, et al. A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin[J]. Nature, 1995, 376(6537):249-253. DOI:10.1038/376249a0 .
[35]	PANKRATZ M J, HOCH M. Control of epithelial morphogenesis by cell signaling and integrin molecules in the Drosophila foregut[J]. Development, 1995, 121(6):1885-1898. DOI:10.1242/dev.121.6.1885 .
[36]	BEIMAN M, SHILO B Z, VOLK T. Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages[J]. Genes Dev, 1996, 10(23):2993-3002. DOI:10.1101/gad.10.23.2993 .
[37]	PIGNONI F, BALDARELLI R M, STEINGRÍMSSON E, et al. The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily[J]. Cell, 1990, 62(1):151-163. DOI:10.1016/0092-8674(90)90249-e .
[38]	GÁLIKOVÁ M, DIESNER M, KLEPSATEL P, et al. Energy homeostasis control in Drosophila adipokinetic hormone mutants[J]. Genetics, 2015, 201(2):665-683. DOI:10.1534/genetics.115.178897 .
[39]	WATERSON M J, CHUNG B Y, HARVANEK Z M, et al. Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling[J]. Proc Natl Acad Sci USA, 2014, 111(22):8137-8142. DOI:10.1073/pnas.1315461111 .
[40]	REINHARD N, BERTOLINI E, SAITO A, et al. The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond[J]. J Comp Neurol, 2022, 530(9):1507-1529. DOI:10.1002/cne.25294 .
[41]	HENTZE J L, CARLSSON M A, KONDO S, et al. The neuropeptide allatostatin a regulates metabolism and feeding decisions in Drosophila [J]. Sci Rep, 2015, 5:11680. DOI:10.1038/srep11680 .
[42]	SCOPELLITI A, BAUER C, YU Y C, et al. A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila [J]. Cell Metab, 2019, 29(2):269-284.e10. DOI:10.1016/j.cmet.2018.09.021 .
[43]	YOSHINARI Y, KOSAKAMOTO H, KAMIYAMA T, et al. The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster [J]. Nat Commun, 2021, 12(1):4818. DOI:10.1038/s41467-021-25146-w .
[44]	NÄSSEL D R, ZANDAWALA M. Hormonal axes in Drosophila: regulation of hormone release and multiplicity of actions[J]. Cell Tissue Res, 2020, 382(2):233-266. DOI:10.1007/s00441-020-03264-z .
[45]	BRACO J T, NELSON J M, SAUNDERS C J, et al. Modulation of metabolic hormone signaling via a circadian hormone and biogenic amine in Drosophila melanogaster [J]. Int J Mol Sci, 2022, 23(8):4266. DOI:10.3390/ijms23084266 .
[46]	JOHNSON E C, SHAFER O T, TRIGG J S, et al. A novel diuretic hormone receptor in Drosophila: evidence for conservation of CGRP signaling[J]. J Exp Biol, 2005, 208(Pt 7):1239-1246. DOI:10.1242/jeb.01529 .
[47]	JOHNSON E C, BOHN L M, BARAK L S, et al. Identification of Drosophila neuropeptide receptors by G protein-coupled receptors-β-arrestin2 interactions[J]. J Biol Chem, 2003, 278(52):52172-52178. DOI:10.1074/jbc.M306756200 .
[48]	POST S, LIAO S F, YAMAMOTO R, et al. Drosophila insulin-like peptide dilp1 increases lifespan and glucagon-like Akh expression epistatic to dilp2[J]. Aging Cell, 2019, 18(1):e12863. DOI:10.1111/acel.12863 .
[49]	AHMAD M, HE L, PERRIMON N. Regulation of insulin and adipokinetic hormone/glucagon production in flies[J]. Wiley Interdiscip Rev Dev Biol, 2020, 9(2):e360. DOI:10.1002/wdev.360 .
[50]	KANNAN K, FRIDELL Y C. Functional implications of Drosophila insulin -like peptides in metabolism, aging, and dietary restriction[J]. Front Physiol, 2013, 4:288. DOI:10.3389/fphys.2013.00288 .
[51]	GÄDE G, AUERSWALD L, MARCO H G. Flight fuel and neuropeptidergic control of fuel mobilisation in the twig wilter, Holopterna alata (Hemiptera, Coreidae)[J]. J Insect Physiol, 2006, 52(11-12):1171-1181. DOI:10.1016/j.jinsphys. 2006.08.005 .
[52]	STEELE J E. Occurrence of a hyperglycæmic factor in the corpus cardiacum of an insect[J]. Nature, 1961, 192(4803):680-681. DOI:10.1038/192680a0 .
[53]	RHEA J M, WEGENER C, BENDER M. The proprotein convertase encoded by amontillado (amon) is required in Drosophila corpora cardiaca endocrine cells producing the glucose regulatory hormone AKH[J]. PLoS Genet, 2010, 6(5):e1000967. DOI:10.1371/journal.pgen.1000967 .
[54]	LORENZ M W, GÄDE G. Hormonal regulation of energy metabolism in insects as a driving force for performance[J]. Integr Comp Biol, 2009, 49(4):380-392. DOI:10.1093/icb/icp019 .
[55]	TOPRAK U. The role of peptide hormones in insect lipid metabolism[J]. Front Physiol, 2020, 11:434. DOI:10.3389/fphys.2020.00434 .
[56]	HEWES R S, TAGHERT P H. Neuropeptides and neuropeptide receptors in the Drosophila melanogaster genome[J]. Genome Res, 2001, 11(6):1126-1142. DOI:10.1101/gr.169901 .
[57]	PARK Y, KIM Y J, ADAMS M E. Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution[J]. Proc Natl Acad Sci USA, 2002, 99(17):11423-11428. DOI:10.1073/pnas.162276199 .
[58]	STAUBLI F, JORGENSEN T J D, CAZZAMALI G, et al. Molecular identification of the insect adipokinetic hormone receptors[J]. Proc Natl Acad Sci USA, 2002, 99(6):3446-3451. DOI:10.1073/pnas.052556499 .
[59]	MARCHAL E, SCHELLENS S, MONJON E, et al. Analysis of peptide ligand specificity of different insect adipokinetic hormone receptors[J]. Int J Mol Sci, 2018, 19(2):542. DOI:10.3390/ijms19020542 .
[60]	ORYAN A, WAHEDI A, PALUZZI J V. Functional characterization and quantitative expression analysis of two GnRH-related peptide receptors in the mosquito, Aedes aegypti [J]. Biochem Biophys Res Commun, 2018, 497(2):550-557. DOI:10.1016/j.bbrc.2018.02.088 .
[61]	ZANDAWALA M, HAMOUDI Z, LANGE A B, et al. Adipokinetic hormone signalling system in the Chagas disease vector, Rhodnius prolixus [J]. Insect Mol Biol, 2015, 24(2):264-276. DOI:10.1111/imb.12157 .
[62]	ALFA R W, PARK S, SKELLY K R, et al. Suppression of insulin production and secretion by a decretin hormone[J]. Cell Metab, 2015, 21(2):323-334. DOI:10.1016/j.cmet.2015.01.006 .
[63]	SLOTH ANDERSEN A, HERTZ HANSEN P, SCHAFFER L, et al. A new secreted insect protein belonging to the immuno globulin superfamily binds insulin and related peptides and inhibits their activities[J]. J Biol Chem, 2000, 275(22):16948-16953. DOI:10.1074/jbc.M001578200 .
[64]	YAMANAKA Y, WILSON E M, ROSENFELD R G, et al. Inhibition of insulin receptor activation by insulin-like growth factor binding proteins[J]. J Biol Chem, 1997, 272(49):30729-30734. DOI:10.1074/jbc.272.49.30729 .
[65]	GARBE J C, YANG E, FRISTROM J W. IMP-L2: an essential secreted immunoglobulin family member implicated in neural and ectodermal development in Drosophila [J]. Development, 1993, 119(4):1237-1250. DOI:10.1242/dev.119. 4.1237 .
[66]	HONEGGER B, GALIC M, KÖHLER K, et al. Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance[J]. J Biol, 2008, 7(3):10. DOI:10.1186/jbiol72 .
[67]	ALIC N, HODDINOTT M P, VINTI G, et al. Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor[J]. Aging Cell, 2011, 10(1):137-147. DOI:10.1111/j.1474-9726.2010.00653.x .
[68]	LAYALLE S, ARQUIER N, LÉOPOLD P. The TOR pathway couples nutrition and developmental timing in Drosophila [J]. Dev Cell, 2008, 15(4):568-577. DOI:10.1016/j.devcel.2008.08.003 .
[69]	COLOMBANI J, BIANCHINI L, LAYALLE S, et al. Antagonistic actions of ecdysone and insulins determine final size in Drosophila [J]. Science, 2005, 310(5748):667-670. DOI:10.1126/science.1119432 .
[70]	SARRAF-ZADEH L, CHRISTEN S, SAUER U, et al. Local requirement of the Drosophila insulin binding protein imp-L2 in coordinating developmental progression with nutritional conditions[J]. Dev Biol, 2013, 381(1):97-106. DOI:10.1016/j.ydbio.2013.06.008 .
[71]	CALDWELL P E, WALKIEWICZ M, STERN M. Ras activity in the Drosophila prothoracic gland regulates body size and developmental rate via ecdysone release[J]. Curr Biol, 2005, 15(20):1785-1795. DOI:10.1016/j.cub.2005.09.011 .
[72]	MIRTH C, TRUMAN J W, RIDDIFORD L M. The role of the prothoracic gland in determining critical weight for metamorphosis in Drosophila melanogaster [J]. Curr Biol, 2005, 15(20):1796-1807. DOI:10.1016/j.cub.2005.09.017 .
[73]	NOYES B E, KATZ F N, SCHAFFER M H. Identification and expression of the Drosophila adipokinetic hormone gene[J]. Mol Cell Endocrinol, 1995, 109(2):133-141. DOI:10.1016/0303-7207(95)03492-p .
[74]	KIM J, NEUFELD T P. Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3[J]. Nat Commun, 2015, 6:6846. DOI:10.1038/ncomms7846 .
[75]	YAMANAKA N, REWITZ K F, O'CONNOR M B. Ecdysone control of developmental transitions: lessons from Drosophila research[J]. Annu Rev Entomol, 2013, 58:497-516. DOI:10.1146/annurev-ento-120811-153608 .
[76]	KIM S K, TSAO D D, SUH G S B, et al. Discovering signaling mechanisms governing metabolism and metabolic diseases with Drosophila [J]. Cell Metab, 2021, 33(7):1279-1292. DOI:10.1016/j.cmet.2021.05.018 .
[77]	GRÖNKE S, MÜLLER G, HIRSCH J, et al. Dual lipolytic control of body fat storage and mobilization in Drosophila [J]. PLoS Biol, 2007, 5(6):e137. DOI:10.1371/journal.pbio.0050137 .
[78]	ARRESE E L, ROJAS-RIVAS B I, WELLS M A. The use of decapitated insects to study lipid mobilization in adult Manduca sexta: effects of adipokinetic hormone and trehalose on fat body lipase activity[J]. Insect Biochem Mol Biol, 1996, 26(8-9):775-782. DOI:10.1016/s0965-1748(96)00024-0 .
[79]	GÄDE G. Activation of fat body glycogen phosphorylase in Locusta migratoria by corpus cardiacum extract and synthetic adipokinetic hormone[J]. J Insect Physiol, 1981, 27(3):155-161. DOI:10.1016/0022-1910(81)90122-0 .
[80]	AUERSWALD L, GÄDE G. Endocrine control of TAG lipase in the fat body of the migratory locust, Locusta migratoria [J]. Insect Biochem Mol Biol, 2006, 36(10):759-768. DOI:10.1016/j.ibmb.2006.07.004 .
[81]	TOMCALA A, BÁRTŮ I, SIMEK P, et al. Locust adipokinetic hormones mobilize diacylglycerols selectively[J]. Comp Biochem Physiol B Biochem Mol Biol, 2010, 156(1):26-32. DOI:10.1016/j.cbpb.2010.01.015 .
[82]	AUERSWALD L, GÄDE G. The role of Ins(1, 4, 5)P(3) in signal transduction of the metabolic neuropeptide Mem-CC in the cetoniid beetle, Pachnoda sinuata [J]. Insect Biochem Mol Biol, 2002, 32(12):1793-1803. DOI:10.1016/s0965-1748(02)00138-8 .
[83]	GÄDE G, AUERSWALD L. Mode of action of neuropeptides from the adipokinetic hormone family[J]. Gen Comp Endocrinol, 2003, 132(1):10-20. DOI:10.1016/s0016-6480(03)00159-x .
[84]	VAN MARREWIJK W J A, VAN DEN BROEK A T M, BEENAKKERS A M TH. Adipokinetic hormone is dependent on extracellular Ca²⁺ for its stimulatory action on the glycogenolytic pathway in locust fat body in vitro [J]. Insect Biochem, 1991, 21(4):375-380. DOI:10.1016/0020-1790(91)90003-W .
[85]	VROEMEN S F, VAN DER HORST D J, VAN MARREWIJK W J. New insights into adipokinetic hormone signaling[J]. Mol Cell Endocrinol, 1998, 141(1-2):7-12. DOI:10.1016/s0303-7207(98)00079-3 .
[86]	YU Y, HUANG R, YE J, et al. Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila [J]. eLife, 2016, 5:e15693. DOI:10.7554/eLife.15693 .
[87]	MOCHANOVÁ M, TOMČALA A, SVOBODOVÁ Z, et al. Role of adipokinetic hormone during starvation in Drosophila [J]. Comp Biochem Physiol B Biochem Mol Biol, 2018, 226:26-35. DOI:10.1016/j.cbpb.2018.08.004 .
[88]	HUANG R, SONG T T, SU H F, et al. High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila [J]. eLife, 2020, 9:e53103. DOI:10.7554/eLife.53103 .
[89]	REWITZ K F, YAMANAKA N, GILBERT L I, et al. The insect neuropeptide PTTH activates receptor tyrosine kinase torso to initiate metamorphosis[J]. Science, 2009, 326(5958):1403-1405. DOI:10.1126/science.1176450 .
[90]	KANG P, LIU P D, HU Y H, et al. NF-κB-mediated developmental delay extends lifespan in Drosophila [J]. Proc Natl Acad Sci USA, 2025, 122(19):e2420811122. DOI:10.1073/pnas.2420811122 .
[91]	JOURJINE N, MULLANEY B C, MANN K, et al. Coupled sensing of hunger and thirst signals balances sugar and water consumption[J]. Cell, 2016, 166(4):855-866. DOI:10.1016/j.cell.2016.06.046 .
[92]	GHOSH S, LENG W H, WILSCH-BRÄUNINGER M, et al. A local insulin reservoir in Drosophila alpha cell homologs ensures developmental progression under nutrient shortage[J]. Curr Biol, 2022, 32(8):1788-1797.e5. DOI:10.1016/j.cub.2022.02.068 .
[93]	STOFFOLANO J G, CROKE K, CHAMBERS J, et al. Role of Phote-HrTH (Phormia terraenovae hypertrehalosemic hormone) in modulating the supercontractile muscles of the crop of adult Phormia regina Meigen[J]. J Insect Physiol, 2014, 71:147-155. DOI:10.1016/j.jinsphys.2014.10.014 .
[94]	BHARUCHA K N, TARR P, ZIPURSKY S L. A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis[J]. J Exp Biol, 2008, 211(Pt 19):3103-3110. DOI:10.1242/jeb.016451 .
[95]	LEBRETON S, MANSOURIAN S, BIGARREAU J, et al. The adipokinetic hormone receptor modulates sexual behavior, pheromone perception and pheromone production in a sex-specific and starvation-dependent manner in Drosophila melanogaster [J]. Front Ecol Evol, 2016, 3:151. DOI:10.3389/fevo.2015.00151 .
[96]	KO K I, ROOT C M, LINDSAY S A, et al. Starvation promotes concerted modulation of appetitive olfactory behavior via parallel neuromodulatory circuits[J]. eLife, 2015, 4:e08298. DOI:10.7554/eLife.08298 .
[97]	ISABEL G, MARTIN J R, CHIDAMI S, et al. AKH-producing neuroendocrine cell ablation decreases trehalose and induces behavioral changes in Drosophila [J]. Am J Physiol Regul Integr Comp Physiol, 2005, 288(2): R531-R538. DOI:10.1152/ajpregu.00158.2004 .
[98]	HOU Q L, CHEN E H, JIANG H B, et al. Adipokinetic hormone receptor gene identification and its role in triacylglycerol mobilization and sexual behavior in the oriental fruit fly (Bactrocera dorsalis)[J]. Insect Biochem Mol Biol, 2017, 90:1-13. DOI:10.1016/j.ibmb.2017.09.006 .
[99]	LU K, ZHANG X Y, CHEN X, et al. Adipokinetic hormone receptor mediates lipid mobilization to regulate starvation resistance in the brown planthopper, Nilaparvata lugens [J]. Front Physiol, 2018, 9:1730. DOI:10.3389/fphys.2018.01730 .
[100]	ZEMANOVÁ M, STAŠKOVÁ T, KODRÍK D. Role of adipokinetic hormone and adenosine in the anti-stress response in Drosophila melanogaster [J]. J Insect Physiol, 2016, 91-92:39-47. DOI:10.1016/j.jinsphys.2016.06.010 .
[101]	HE Q K, DU J, WEI L Y, et al. AKH-FOXO pathway regulates starvation-induced sleep loss through remodeling of the small ventral lateral neuron dorsal projections[J]. PLoS Genet, 2020, 16(10):e1009181. DOI:10.1371/journal.pgen.1009181 .
[102]	HONG S H, LEE K S, KWAK S J, et al. Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals[J]. PLoS Genet, 2012, 8(8):e1002857. DOI:10.1371/journal.pgen.1002857 .
[103]	GUNTUR A R, GU P Y, TAKLE K, et al. Drosophila TRPA1 isoforms detect UV light via photochemical production of H₂O₂ [J]. Proc Natl Acad Sci USA, 2015, 112(42):E5753-E5761. DOI:10.1073/pnas.1514862112 .
[104]	INAGAKI H K, PANSE K M, ANDERSON D J. Independent, reciprocal neuromodulatory control of sweet and bitter taste sensitivity during starvation in Drosophila [J]. Neuron, 2014, 84(4):806-820. DOI:10.1016/j.neuron.2014.09.032 .
[105]	ARRESE E L, SOULAGES J L. Insect fat body: energy, metabolism, and regulation[J]. Annu Rev Entomol, 2010, 55:207-225. DOI:10.1146/annurev-ento-112408-085356 .
[106]	CHOI S, LIM D S, CHUNG J. Feeding and fasting signals converge on the LKB1-SIK3 pathway to regulate lipid metabolism in Drosophila [J]. PLoS Genet, 2015, 11(5):e1005263. DOI:10.1371/journal.pgen.1005263 .