S2 cells were transfected with eYFP-tagged capaR, left un-treated or treated with capa-1, and viewed by confocal microscopy after immunocytochemistry with anti-GFP antibody. (A) Control. (B) capa-1 stimulated, 15 min. (C) sample was incubated for 15 minutes with capa-1, washed three times with culture medium followed by 30 minutes incubation in culture medium to allow resensitization. Nuclei are labelled blue with DAPI, scale bar represents 10 µM. (D) S2 cells expressing capaR were left untreated (0), or treated for 5, 10, 20 or 30 minutes (indicated) with 10−7 M capa-1 to induce receptor internalization. An additional sample was incubated for 30 minutes with capa-1, washed three times with culture medium without capa-1 followed by 30 minutes incubation in culture medium to allow resensitization (Res.). A sample of untransfected cells serves as a negative control. Samples were subjected to cell surface biotinylation to label plasma membrane proteins. We found that the protein concentration of biotinylated samples are generally lower than that of the total lysates; therefore, the equivalent of 5000 cells were loaded for the total lysate, and an equivalent of 15,000 cells were loaded for the biotinylated samples. Total lysates and biotinylated samples were subjected to western blot analysis. Immunoblot using anti-capaR antibody identified a band of the predicted size of 52 kDa which confirms the specificity of the antibody and an additional non specific 75 kDa protein absent in the cell-surface (biotinylated) fraction. (E) Samples from the cell surface biotinylation experiment were semi-quantified and corrected for total receptor expression. Relative cell surface expression is shown as a percentage of the non-treated S2 cells expressing capaR (t = 0). Bars indicated with an asterisk were significantly (P<0.05 as determined by one-way ANOVA) reduced compared to t = 0. (F) Calcium measurements in S2 cells transfected with expression constructs for aequorin and the capa receptor. S2 cells were challenged with 10−7 M capa-1, pre-treated with capa-1 for 15 min (Desensitization (Des.)), followed by ligand removal after which S2 cells were challenged at 15 min or 30 min (Resensitization (Res.)) with 10−7 M capa-1 and cytosolic [Ca2+]i levels measured. Bars indicated with an asterisk were significantly (P<0.05 as determined by Student's t-test) reduced compared to control. (G) Analysis of capaR-β-arrestin-2 interactions. S2 cells were co-transfected with capa receptor tagged with Renilla luciferase and β-arrestin-2 tagged with eYFP. Bioluminescence Resonance Energy Transfer (BRET) signals were monitored after treatment of the cells for 15 min with varying concentrations of capa-1. Data are expressed as mBRET units ± SEM, N = 3.

S2 cells were transfected with eYFP-tagged capaR, left un-treated or treated with capa-1, and viewed by confocal microscopy after immunocytochemistry with anti-GFP antibody. (A) Control. (B) capa-1 stimulated, 15 min. (C) sample was incubated for 15 minutes with capa-1, washed three times with culture medium followed by 30 minutes incubation in culture medium to allow resensitization. Nuclei are labelled blue with DAPI, scale bar represents 10 µM. (D) S2 cells expressing capaR were left untreated (0), or treated for 5, 10, 20 or 30 minutes (indicated) with 10−7 M capa-1 to induce receptor internalization. An additional sample was incubated for 30 minutes with capa-1, washed three times with culture medium without capa-1 followed by 30 minutes incubation in culture medium to allow resensitization (Res.). A sample of untransfected cells serves as a negative control. Samples were subjected to cell surface biotinylation to label plasma membrane proteins. We found that the protein concentration of biotinylated samples are generally lower than that of the total lysates; therefore, the equivalent of 5000 cells were loaded for the total lysate, and an equivalent of 15,000 cells were loaded for the biotinylated samples. Total lysates and biotinylated samples were subjected to western blot analysis. Immunoblot using anti-capaR antibody identified a band of the predicted size of 52 kDa which confirms the specificity of the antibody and an additional non specific 75 kDa protein absent in the cell-surface (biotinylated) fraction. (E) Samples from the cell surface biotinylation experiment were semi-quantified and corrected for total receptor expression. Relative cell surface expression is shown as a percentage of the non-treated S2 cells expressing capaR (t = 0). Bars indicated with an asterisk were significantly (P<0.05 as determined by one-way ANOVA) reduced compared to t = 0. (F) Calcium measurements in S2 cells transfected with expression constructs for aequorin and the capa receptor. S2 cells were challenged with 10−7 M capa-1, pre-treated with capa-1 for 15 min (Desensitization (Des.)), followed by ligand removal after which S2 cells were challenged at 15 min or 30 min (Resensitization (Res.)) with 10−7 M capa-1 and cytosolic [Ca2+]i levels measured. Bars indicated with an asterisk were significantly (P<0.05 as determined by Student's t-test) reduced compared to control. (G) Analysis of capaR-β-arrestin-2 interactions. S2 cells were co-transfected with capa receptor tagged with Renilla luciferase and β-arrestin-2 tagged with eYFP. Bioluminescence Resonance Energy Transfer (BRET) signals were monitored after treatment of the cells for 15 min with varying concentrations of capa-1. Data are expressed as mBRET units ± SEM, N = 3.

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The capa peptide receptor, capaR (CG14575), is a G-protein coupled receptor (GPCR) for the D. melanogaster capa neuropeptides, Drm-capa-1 and -2 (capa-1 and -2). To date, the capa peptide family constitutes the only known nitridergic peptides in insects, so the mechanisms and physiological function of ligand-receptor signalling of this peptide fami...

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... Insect CAPA neuropeptides are produced in the central nervous system and are evolutionarily related to neuromedin U in vertebrates (8). In the fruit fly, Drosophila melanogaster, CAPA peptides have been shown to act through a conserved nitridergic signaling pathway to stimulate diuresis by MTs (9,10); however, a few other studies have alluded to an antidiuretic role (11,12). In contrast, in both larval and adult A. aegypti, CAPA peptides inhibit fluid secretion through a signaling cascade involving the NOS/ cGMP/PKG pathway (6,7). ...
... Our study provides evidence that the antidiuretic activity of CAPA is mediated through the dissociation of the VA holoenzyme involving the removal of the V 1 complex from the apical membrane, hindering luminal flux of protons that in turn starves cation/H + exchange, which ultimately reduces fluid secretion (Fig. 6). CAPA peptides are known to elicit both diuretic and antidiuretic actions in different insects, whereby a stimulatory role has been established in D. melanogaster (9,10) and inhibitory in the R. prolixus (65) and D. melanogaster (11,12) indicating a species-specific role of this neuropeptide family, which may be due to their different diets and lifestyles. Given the unique blood-feeding stress the female mosquito is subjected to, a carefully controlled mechanism of both diuretic and antidiuretic hormones is warranted to rid the haemolymph of excess salts and water while also preventing the female from excessive secretion. ...
... In summary, our study highlights a target in the antidiuretic signaling pathway of adult female A. aegypti MTs, emphasizing the intricate and precise regulatory mechanism of antidiuresis. Although a plethora studies have investigated the process of hydromineral balance in terrestrial insects from a diuretic perspective (1,10,23,65,(69)(70)(71), these current findings advance our understanding of antidiuretic hormone control while providing further evidence of a previously elusive endocrine regulatory mechanism of the VA in mosquitoes (Fig. 6). Given that many insects are recognized as agricultural pests or disease vectors, further investigating the complex regulation of their ionic and osmotic balance may aid in lessening their burden on human health and prosperity through development of improved management strategies that, at least in part, impede their neuroendocrine control of hydromineral homeostasis. ...
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Like other insects, secretion by mosquito Malpighian tubules (MTs) is driven by the V-type H ⁺ -ATPase (VA) localized in the apical membrane of principal cells. In Aedes aegypti , the antidiuretic neurohormone CAPA inhibits secretion by MTs stimulated by select diuretic hormones; however, the cellular effectors of this inhibitory signaling cascade remain unclear. Herein, we demonstrate that the VA inhibitor bafilomycin selectively inhibits serotonin (5HT)- and calcitonin-related diuretic hormone (DH 31 )-stimulated secretion. VA activity increases in DH 31 -treated MTs, whereas CAPA abolishes this increase through a NOS/cGMP/PKG signaling pathway. A critical feature of VA activation involves the reversible association of the cytosolic (V 1 ) and membrane (V o ) complexes. Indeed, higher V 1 protein abundance was found in membrane fractions of DH 31 -treated MTs, whereas CAPA significantly decreased V 1 abundance in membrane fractions while increasing it in cytosolic fractions. V 1 immunolocalization was observed strictly in the apical membrane of DH 31 -treated MTs, whereas immunoreactivity was dispersed following CAPA treatment. VA complexes colocalized apically in female MTs shortly after a blood meal consistent with the peak and postpeak phases of diuresis. Comparatively, V 1 immunoreactivity in MTs was more dispersed and did not colocalize with the V o complex in the apical membrane at 3 h post blood meal, representing a time point after the late phase of diuresis has concluded. Therefore, CAPA inhibition of MTs involves reducing VA activity and promotes complex dissociation hindering secretion. Collectively, these findings reveal a key target in hormone-mediated inhibition of MTs countering diuresis that provides a deeper understanding of this critical physiological process necessary for hydromineral balance.
... There are several genome-wide studies investigating the underlying genetic architecture of desiccation tolerance in D. melanogaster [32,[37][38][39][40]. However, knowledge on the genome-wide transcriptomic response is still limited, as most studies focused on the analysis of a few candidate genes in laboratory selected lines [41][42][43][44][45][46]. Transcriptomic analysis are relevant as they allow to identify changes in gene expression that can be due to genetic and epigenetic variation, as well as informing on the biological processes affected by the studied condition. ...
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Background Climate change is one of the main factors shaping the distribution and biodiversity of organisms, among others by greatly altering water availability, thus exposing species and ecosystems to harsh desiccation conditions. However, most of the studies so far have focused on the effects of increased temperature. Integrating transcriptomics and physiology is key to advancing our knowledge on how species cope with desiccation stress, and these studies are still best accomplished in model organisms. Results Here, we characterized the natural variation of European D. melanogaster populations across climate zones and found that strains from arid regions were similar or more tolerant to desiccation compared with strains from temperate regions. Tolerant and sensitive strains differed not only in their transcriptomic response to stress but also in their basal expression levels. We further showed that gene expression changes in tolerant strains correlated with their physiological response to desiccation stress and with their cuticular hydrocarbon composition, and functionally validated three of the candidate genes identified. Transposable elements, which are known to influence stress response across organisms, were not found to be enriched nearby differentially expressed genes. Finally, we identified several tRNA-derived small RNA fragments that differentially targeted genes in response to desiccation stress. Conclusions Overall, our results showed that basal gene expression differences across individuals should be analyzed if we are to understand the genetic basis of differential stress survival. Moreover, tRNA-derived small RNA fragments appear to be relevant across stress responses and allow for the identification of stress-response genes not detected at the transcriptional level.
... Based on sequence homology and constructional similarity, GPCRs are mainly categorized into four families in insects, including rhodopsinlike receptors (Family A), secretin-like receptors (Family B), metabotropic glutamate-like receptors (Family C), and atypical 7 TM proteins (Family D) [17]. Since GPCRs are involved in the regulation of many important physiological processes in insects, such as development [18][19][20][21], reproduction [22,23], metabolism [24][25][26], and behaviors [27][28][29], the identification of GPCRs in insects is vital for further exploring their functions and developing novel insecticides. In the last two decades, with the advancement of sequencing technology, many GPCRs have been systematically identified and annotated in insects, including Drosophila melanogaster [17], Acyrthosiphon pisum [30], Aphis craccivora [31], Diaphorina citri [32], Nilaparvata lugens [33], Rhodnius prolixus [34], and Apolygus lucorum [35]. ...
Article
G protein-coupled receptors play important roles in mediating signal transformation and physiological processes. As a new type of insecticide target, GPCRs have attracted much attention in recent years. However, GPCRs have not yet been identified in Aphis gossypii. In the present study, a total of 87 GPCRs were identified from A. gossypii, including 65 Family A, 12 Family B, 7 Family C, and 3 Family F receptors. Most of the GPCRs in A. gossypii showed considerable sequence identity, and all of them have conserved transformmembrane domains. Newly identified GPCR genes were differentially expressed in different developmental stages and tissues. Moreover, we found that 34 GPCR genes were highly overexpressed in a sulfoxaflor-resistant strain, 4 and 10 of them were highly induced by LC15 and LC50 of sulfoxaflor, respectively. Furthermore, silencing of two highly overexpressed GPCRs by RNAi indicated that suppression the expression of AgoGPCR48 and AgoGPCR53 significantly increased the susceptibility of A. gossypii to sulfoxaflor, suggesting that these GPCR genes may be associated with sulfoxaflor resistance in A. gossypii. Our results imply that the overexpression of GPCR genes contribute to the sulfoxaflor resistance development in A. gossypii and provide useful targets for developing novel insecticides to manage this pest.
... The BtabCAPAr gene expression has been recorded to express exclusively in insect Malpighian tubules in both larval and adult stages 41 . The CAPAr mRNA expression was found to be 150 folds more in Malpighian tubules of A. aegypti in comparison to the midgut, hindgut, and reproductive tissues 25 . ...
... A similar CAPAr gene expression trend was observed for H. halys (HalhaCAPA-R), where the highest expression was observed for the 5th nymphal instar and an adult female whereas the egg stage showed the least mRNA transcript levels of the CAPAr gene 31 . The CAPAr gene was expressed 42 and 14.4 fold higher in Malpighian tubules of adult and larvae of D. melanogaster, respectively 41 . However, CAPAr gene expression levels in the larval and pupal stages of A. aegypti remained the same 25 . ...
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The diuresis process in insects is under the regulation of CAPA neuropeptides, which activate the specific cognate receptor i.e CAPAr. In this study, we characterized the CAPAr gene ( BtabCAPAr ) in whitefly, Bemisia tabaci Asia II 1 for the first time. The two splicing isoforms of the BtabCAPAr gene i.e BtabCAPAr -1 and BtabCAPAr -2 which included six (421 aa) and five (355 aa) exons, respectively were recorded. The third exon was missing in the BtabCAPAr -2 isoform as compared to the BtabCAPAr -1 isoform. The transmembrane topology depicted the presence of seven and five transmembrane regions in BtabCAPAr -1 and BtabCAPAr -2, respectively. The relative BtabCAPAr gene expression in different whitefly life stages revealed the highest (3.76 folds) expression level of the BtabCAPAr gene in the adult stage as compared to the egg stage. The expression of the BtabCAPAr gene in the nymphal and pupal stage was found to be on a par with each other as well as egg stage. Two CAPA peptides, CAPA-PVK1 and CAPA-PVK2 were identified through a functional luminescence assay, which strongly activated the BtabCAPAr -1 receptor with very low EC 50 values of 0.067 nM and 0.053 nM, respectively. The basic information generated in the study will help develop biostable peptides, which can be tested further and may lead to the development of new generation insecticides.
... The BtabCAPAr gene expression has been recorded to express exclusively in insect Malpighian tubules in both larval and adult stages 41 . The CAPAr mRNA expression was found to be 150 folds more in Malpighian tubules of A. aegypti in comparison to the midgut, hindgut, and reproductive tissues 25 . ...
Preprint
Full-text available
The diuresis process in insects is regulated by CAPA neuropeptides, which activate the specific cognate receptor i.e CAPAr. In this study, we characterized the CAPAr gene ( BtabCAPAr ) in whitefly, Bemisia tabaci Asia II 1 for the first time. The two splicing isoforms of the BtabCAPAr gene i.e BtabCAPAr -1 and BtabCAPAr -2 which included six (421 aa) and five (355 aa) exons, respectively were recorded. The third exon was missing in the BtabCAPAr -2 isoform. The transmembrane topology depicted the presence of seven and five transmembrane regions in BtabCAPAr -1 and BtabCAPAr -2, respectively. The relative BtabCAPAr gene expression in different whitefly life stages revealed the highest (3.76 folds) expression level of the BtabCAPAr gene in the adult stage as compared to the egg stage. The expression of the BtabCAPAr gene in the nymphal and pupal stage did not differ significantly with each other as well as egg stage. Two peptides, CAPA-PVK1 and CAPA-PVK2 were identified through a functional luminescence assay, which strongly activated the BtabCAPAr -1 receptor with very low EC 50 values of 0.067 nM and 0.053 nM, respectively. The basic information generated in the study will help develop biostable peptides, which can be tested further and may lead to the development of new generation insecticides.
... Drm-capa-1 and Drm-capa-2. Upon silencing of the targeted receptor (capaR) through RNAi, a significant reduction in Ca 2+ ions and fluid secretion was recorded (Terhzaz et al., 2012). In an another study, silencing of capa gene (encoding for neuropeptides) in adult D. melanogaster, resulted into reduced mRNA transcript levels by approximately 90% when compared to control and as a result of reduced expression of capa gene, knock down flies survived longer under the desiccation stress due to decrease in rate of water loss or reduced diuresis (Terhzaz et al., 2015). ...
Article
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Bemisia tabaci (Gennadius) Asia II 1 cause significant economic losses to cotton crop, directly by feeding on sap and indirectly through virus transmission. Although the current control methods are the combination of different tactics but still the chemical control is heavily relied. B. tabaci has gained resistance to majority of the insecticides which has made it difficult to manage this pest using synthetic chemicals. RNAi based gene silencing has been evolved as potential biochemical tool for specific gene silencing of target insect-pest and has been successfully demonstrated for Hemipteran insects. Here, we report the successful silencing of the CAPAr gene in B. tabaci which encodes for the G-protein coupled receptor (a transmembrane membrane peptide). Silencing of CAPAr gene resulted into reduced survival and fecundity of B. tabaci. Oral delivery of dsRNA mediated artificial diet corresponding to CAPAr gene resulted into significantly high adult mortality of 30.74% in treatment dsCAPAr 1.0 µg/µl after 48 hr of dsRNA feeding. A significant reduction in whitefly female fecundity was recorded for all the dsCAPAr concentrations with lowest value of 53.51 eggs per female in dsCAPAr 1.0 µg/µl. The relative gene expression of CAPAr gene further confirms the down regulation of CAPAr gene in knock down adult whiteflies. Our investigation proves the importance of CAPAr for B. tabaci survival and may be exploited as potential tool which can be strategic in integrated management programme for B. tabaci.
... The larger and more numerous principal cells are involved in electrogenic cation (Na + , K + ) secretion that is energized by an apical vacuolar-type H + -ATPase. Cation transport through principal cells is stimulated by diuretic hormones (DHs) which include functional homologs of the vertebrate corticotropin releasing factor (CRF) and calcitonin gene-related peptide (CGRP) families, as well as the capa peptides which share with to the vertebrate neuromedin U peptides (Cabrero et al., 2002;Coast et al., 2001;Terhzaz et al., 2012). The smaller, less numerous secondary cells are intercalated among the tubule principal cells. ...
Article
This Review addresses the means by which epithelia change the direction of vectorial ion transport. Recent studies have revealed that insect Malpighian (renal) tubules can switch from secreting to reabsorbing K+. When the gut of larval lepidopterans is empty (during the moult cycle) or when the larvae are reared on K+-deficient diet, the distal ileac plexus segment of the tubule secretes K+ from the haemolymph into the tubule lumen. By contrast, in larvae reared on K+-rich diet, ions and fluid are reabsorbed from the rectal lumen into the perinephric space surrounding the cryptonephridial tubules of the rectal complex. Ions and fluid are then transported from the perinephric space into the lumen of the cryptonephridial tubules, thus supplying the free segments of the tubule downstream. Under these conditions, some of the K+ and water in the tubule lumen is reabsorbed across the cells of the distal ileac plexus, allowing for expansion of haemolymph volume in the rapidly growing larvae, as well as recycling of K+ and base equivalents. RNA sequencing data reveal large-scale changes in gene transcription that are associated with the switch between ion secretion and ion reabsorption by the distal ileac plexus. An unexpected finding is the presence of voltage-gated, ligand-gated and mechanosensitive ion channels, normally seen in excitable cells, in Malpighian tubules. Transcriptomic surveys indicate that these types of channels are also present in multiple other types of vertebrate and invertebrate epithelia, suggesting that they may play novel roles in epithelial cell signalling and regulation of epithelial ion transport.
... Moreover, 5-HT7 and Dop2R were shown to be associated with learning ability (77,78) and octopamine receptors were required for ovulation in D. melanogaster (79). The ligands of neuropeptide and protein hormone receptors and the B1 subfamily belong to neuropeptides, which also play an important role in the regulation of development, reproduction, feeding, courtship, aggression, olfaction, locomotor activity, circadian rhythm, and many other physiological processes in insects (21,80,81). The gene expansion of these three subfamilies indicated that A. lucorum had a more complex peptidergic signaling system. ...
Article
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Spodoptera frugiperda (Insecta: Lepidoptera) is a destructive invasive pest feeding on various plants and causing serious damage to several economically-important crops. G protein-coupled receptors (GPCRs) are cellular receptors that coordinate diverse signaling processes, associated with many physiological processes and disease states. However, less information about GPCRs had been reported in S. frugiperda, limiting the recognition of signaling system and in-depth studies of this pest. Here, a total of 167 GPCRs were identified in S. frugiperda. Compared with other insects, the GPCRs of S. frugiperda were significantly expanded. A large of tandem duplication and segmental duplication events were observed, which may be the key factor to increase the size of GPCR family. In detail, these expansion events mainly concentrate on biogenic amine receptors, neuropeptide and protein hormone receptors, which may be involved in feeding, reproduction, life span, and tolerance of S. frugiperda. Additionally, 17 Mth/Mthl members were identified in S. frugiperda, which may be similar to the evolutionary pattern of 16 Mth/Mthl members in Drosophila. Moreover, the expression patterns across different developmental stages of all GPCR genes were also analyzed. Among these, most of the GPCR genes are poorly expressed in S. frugiperda and some highly expressed GPCR genes help S. frugiperda adapt to the environment better, such as Rh6 and AkhR. In this study, all GPCRs in S. frugiperda were identified for the first time, which provided a basis for further revealing the role of these receptors in the physiological and behavioral regulation of this pest.
... Moreover, 5-HT7 and Dop2R were shown to be associated with learning ability (77,78) and octopamine receptors were required for ovulation in D. melanogaster (79). The ligands of neuropeptide and protein hormone receptors and the B1 subfamily belong to neuropeptides, which also play an important role in the regulation of development, reproduction, feeding, courtship, aggression, olfaction, locomotor activity, circadian rhythm, and many other physiological processes in insects (21,80,81). The gene expansion of these three subfamilies indicated that A. lucorum had a more complex peptidergic signaling system. ...
Article
Full-text available
G protein-coupled receptors (GPCRs) are the largest and most versatile family of transmembrane receptors in the cell and they play a vital role in the regulation of multiple physiological processes. The family Miridae (Hemiptera: Heteroptera) is one of the most diverse families of insects. Until now, information on GPCRs has been lacking in Miridae. Apolygus lucorum, a representative species of the Miridae, is an omnivorous pest that occurs worldwide and is notorious for causing serious damage to various crops and substantial economic losses. By searching the genome, 133 GPCRs were identified in A. lucorum. Compared with other model insects, we have observed GPCR genes to be remarkably expanded in A. lucorum, especially focusing on biogenic amine receptors and neuropeptide receptors. Among these, there is a novel large clade duplicated from known FMRFamide receptors (FMRFaRs). Moreover, the temporal and spatial expression profiles of the 133 genes across developmental stages were determined by transcriptome analysis. Most GPCR genes showed a low expression level in the whole organism of A. lucorum. However, there were a few highly expressed GPCR genes. The highly expressed LW opsins in the head probably relate to nocturning of A. lucorum, and the expression of Cirl at different times and in different tissues indicated it may be involved in growth and development of A. lucorum. We also found C2 leucine-rich repeat-containing GPCRs (LGRs) were mainly distributed in Hemiptera and Phthiraptera among insects. Our study was the first investigation on GPCRs in A. lucorum and it provided a molecular target for the regulation and control of Miridae pests.
... Its name comes from the cardioacceleratory properties and stimulation of contraction of visceral muscles. However, most research suggests that these neurohormones are primarily involved in regulation of insect diuresis [171][172][173][174][175][176][177][178][179][180][181]. ...
... Research by Terhzaz, et al. [172] confirms that not only are hugins the NMU homologues, but also insect CAPA-PVK neuropeptides. In this research, authors present that vertebrate NMU is a putative functional homolog of Drome-CAPA-1 and -2. ...
Article
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Nowadays, one of the biggest problems in healthcare is an obesity epidemic. Consumption of cheap and low-quality energy-rich diets, low physical activity, and sedentary work favor an increase in the number of obesity cases within many populations/nations. This is a burden on society, public health, and the economy with many deleterious consequences. Thus, studies concerning this disorder are extremely needed, including searching for new, effective, and fitting models. Obesity may be related, among other factors, to disrupting adipocytes activity, disturbance of metabolic homeostasis, dysregulation of hormonal balance, cardiovascular problems, or disorders in nutrition which may lead to death. Because of the high complexity of obesity, it is not easy to find an ideal model for its studies which will be suitable for genetic and physiological analysis including specification of different compounds’ (hormones, neuropeptides) functions, as well as for signaling pathways analysis. In recent times, in search of new models for human diseases there has been more and more attention paid to insects, especially in neuro-endocrine regulation. It seems that this group of animals might also be a new model for human obesity. There are many arguments that insects are a good, multidirectional, and complex model for this disease. For example, insect models can have similar conservative signaling pathways (e.g., JAK-STAT signaling pathway), the presence of similar hormonal axis (e.g., brain–gut axis), or occurrence of structural and functional homologues between neuropeptides (e.g., neuropeptide F and human neuropeptide Y, insulin-like peptides, and human insulin) compared to humans. Here we give a hint to use insects as a model for obesity that can be used in multiple ways: as a source of genetic and peptidomic data about etiology and development correlated with obesity occurrence as well as a model for novel hormonal-based drug activity and their impact on mechanism of disease occurrence.