Drosophila Short Neuropeptide F Regulates Food Intake and Body Size

Abstract

Neuropeptides regulate a wide range of animal behavior including food consumption, circadian rhythms, and anxiety. Recently, Drosophila neuropeptide F, which is the homolog of the vertebrate neuropeptide Y, was cloned, and the function of Drosophila neuropeptide F in feeding behaviors was well characterized. However, the function of the structurally related short neuropeptide F (sNPF) was unknown. Here, we report the cloning, RNA, and peptide localizations, and functional characterizations of the Drosophila sNPF gene. The sNPF gene encodes the preprotein containing putative RLRF amide peptides and was expressed in the nervous system of late stage embryos and larvae. The embryonic and larval localization of the sNPF peptide in the nervous systems revealed the larval central nervous system neural circuit from the neurons in the brain to thoracic axons and to connective axons in the ventral ganglion. In the adult brain, the sNPF peptide was localized in the medulla and the mushroom body. However, the sNPF peptide was not detected in the gut. The sNPF mRNA and the peptide were expressed during all developmental stages from embryo to adult. From the feeding assay, the gainof-function sNPF mutants expressed in nervous systems promoted food intake, whereas the loss-of-function mutants suppressed food intake. Also, sNPF overexpression in nervous systems produced bigger and heavier flies. These findings indicate that the sNPF is expressed in the nervous systems to control food intake and regulate body size in Drosophila melanogaster.Neuropeptides regulate a wide range of animal behavior. In vertebrates, neuropeptide Y (NPY) 1 regulates food consumption, circadian rhythms, anxiety, and other physiological processes (1). NPY, a 36-amino acid neuromodulator, is expressed abundantly in the mammalian brain and controls feeding (2). The NPY injection into the hypothalamus of rat brain resulted in hyperphagia and obesity, whereas the NPY-deficient mouse in the leptin mutant background (NPYϪ/Ϫ; ob/ob) showed the less obese phenotype (3).In invertebrates, neuropeptide F (NPF) peptides share structural similarity with the vertebrate NPY (4). NPF peptides isolated from various invertebrate animals have the conserved (A/L)R(P/L)RF amide sequence at their C-terminal ends (5, 6). From a completely sequenced Drosophila melanogaster genome, short NPF (sNPF; CG13968) and Drosophila NPF (dNPF; CG10342) were found. The dNPF peptide was isolated by the radioimmunoassay. The preprotein is processed to the 36-amino acid peptide containing RVRF amide in the C terminus. dNPF is considered the homolog of the vertebrate NPY. dNPF mRNA and peptide are expressed in the brain and midgut of Drosophila larvae and adults (7). The dNPF neural network in the larval central nervous system (CNS) is changed by the gustatory stimulation of sugar, indicating that dNPF is an integral part of the chemosensory system that regulates eating behavior (8). Drosophila larvae eat continuously and grow in a relatively short period. About 5 days after egg laying, they s...

Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila

“…NPF has also been implicated in regulating feeding behavior in Drosophila (Lee et al 2004), where increases in food intake are correlated with but not completely dependent on post-mating increases in female egg laying (Carvalho et al 2006;Apger-Mcglaughon and Wolfner 2013). Another candidate, allatostatin A (AstA), has been implicated in regulating oviduct muscle contraction in other arthropods (Donini and Lange 2002;Garside et al 2002;Woodhead et al 2003).…”

Processed short neuropeptide F peptides regulate growth through the ERK‐insulin pathway in Drosophila melanogaster

“…In Drosophila melanogaster, sNPF regulates body size and food intake [4]. In order to regulate body size, sNPF produced in the fly brain binds to the sNPF receptor (sNPFR1) and activates extracellular signal-related-kinase (ERK), which turns on the Drosophila insulin-like peptide (Dilp) genes in the insulin producing cells of the brain.…”

“…It may produce sNPF1 (AQRSPSLRLRFa), sNPF2 (WFGDV NQKPIRSPSLRLRFa), sNPF3 (PQRLRWa), and sNPF4 (PMRLRWa) peptides by cleaving flanking dibasic amino acids and amidating in their C-termini [4] (Fig. 2A).…”

“…The short neuropeptide F (sNPF) gene has been found in diverse insect families which include fruit flies, locusts, fire ants, potato beetles, and mosquitoes [1][2][3][4][5]. sNPF regulates various physiological processes like the reproduction in locusts [1], feeding behavior in fire ants [2], and adult diapause in the Colorado potato beetles [3].…”

Molecular physiology of crustacean and insect neuropeptides

“…In Drosophila larvae, sNPFs are expressed in the neurons of the brain (dorsal posterior region) and in the ventral ganglion, while in adults they are present in the medulla and the mushroom bodies. 99) sNPFs regulate food intake and body size 99,100) as determined by elegant ectopic overexpression and knockdown of the sNPF gene. The role of sNPFs on food intake might also be conserved in the hymenopteran Solenopsis invicta.…”