A gut-derived hormone suppresses sugar appetite and regulates food choice in Drosophila

Nature Metabolism, Год журнала: 2022, Номер 4(11), С. 1532 - 1550

Опубликована: Ноя. 7, 2022

Abstract Animals must adapt their dietary choices to meet nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviours is poorly understood. Here we show enteroendocrine cells of the adult female Drosophila midgut sense nutrients in response release neuropeptide F (NPF), which an ortholog mammalian Y-family gut-brain hormones. Gut-derived NPF acts on glucagon-like adipokinetic hormone (AKH) signalling induce sugar satiety increase consumption protein-rich food, adipose tissue promote storage ingested nutrients. Suppression NPF-mediated gut leads overconsumption while simultaneously decreasing intake yeast. Furthermore, gut-derived has a female-specific function promoting protein-containing food mated females. Together, our findings suggest NPF-to-AKH modulates specific regulates choice ensure homeostatic nutrients, providing insight hormonal mechanisms underlie hungers.

Язык: Английский

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The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Фев. 4, 2022

Abstract The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs coordinate systemic energy balance. However, gut-derived hormones affecting behavioral responses poorly defined. Here we show that endocrine cells Drosophila gut sense nutrient stress mechanism involves TOR pathway in response secrete peptide hormone allatostatin C, somatostatin homolog. Gut-derived C induces secretion glucagon-like adipokinetic food intake mobilization. Loss Allatostatin or its receptor adipokinetic-hormone-producing impairs lipid sugar mobilization during fasting, leading hypoglycemia. Our findings illustrate nutrient-responsive maintains homeostasis under nutrient-stress conditions, function essential health whose failure can lead disorders.

Язык: Английский

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Microbes affect gut epithelial cell composition through immune-dependent regulation of intestinal stem cell differentiation

Cell Reports, Год журнала: 2022, Номер 38(13), С. 110572 - 110572

Опубликована: Март 1, 2022

Gut microbes play important roles in host physiology; however, the mechanisms underlying their impact remain poorly characterized. Here, we demonstrate that not only influence gut physiology but also alter its epithelial composition. The microbiota and pathogens both intestinal stem cell (ISC) differentiation. Intriguingly, while promotes ISC differentiation into enterocytes (EC), stimulate enteroendocrine (EE) fate long-term accumulation of EEs midgut epithelium. Importantly, evolutionarily conserved Drosophila NFKB (Relish) pushes lineage specification toward ECs by directly regulating factors. Conversely, JAK-STAT pathway EE response to infectious damage. We propose a model which balance microbial pattern recognition pathways, such as Imd-Relish, damage JAK-STAT, differentiation, composition, physiology.

Язык: Английский

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A phosphate-sensing organelle regulates phosphate and tissue homeostasis

Nature, Год журнала: 2023, Номер 617(7962), С. 798 - 806

Опубликована: Май 3, 2023

Язык: Английский

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split-intein Gal4 provides intersectional genetic labeling that is repressible by Gal80

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(24)

Опубликована: Июнь 5, 2023

The split-Gal4 system allows for intersectional genetic labeling of highly specific cell types and tissues in Drosophila. However, the existing system, unlike standard Gal4 cannot be repressed by Gal80, therefore controlled temporally. This lack temporal control precludes experiments which a manipulation must restricted to timepoints. Here, we describe based on self-excising split-intein, drives transgene expression as strongly current reagents, yet is repressible Gal80. We demonstrate potent inducibility "split-intein Gal4" vivo using both fluorescent reporters via reversible tumor induction gut. Further, show that our split-intein can extended drug-inducible GeneSwitch providing an independent method with inducible control. also used generate type-specific drivers silico predictions generated single-cell RNAseq (scRNAseq) datasets, algorithm ("Two Against Background" or TAB) predict cluster-specific gene pairs across multiple tissue-specific scRNA datasets. provide plasmid toolkit efficiently create either CRISPR knock-ins target genes enhancer fragments. Altogether, creation are inducible/repressible.

Язык: Английский

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The role of Drosophila microbiota in gut homeostasis and immunity

Gut Microbes, Год журнала: 2023, Номер 15(1)

Опубликована: Май 2, 2023

The gut epithelia of virtually all animals harbor complex microbial communities that play an important role in maintaining immune and cellular homeostasis. Gut microbiota have evolutionarily adapted to the host environment, serving as key regulators intestinal stem cells promote a healthy barrier modulate epithelial self-renewal. Disruption these populations has been associated with inflammatory disorders or cancerous lesions intestine. However, molecular mechanisms controlling gut-microbe interactions are only partially understood due high diversity biologically dynamic nature microorganisms. This article reviews current knowledge on Drosophila its signaling pathways crucial for induction distinct homeostatic responses. Thanks genetic tractability cultivable simple microbiota, this association model offers new efficient tools investigating crosstalk between while providing framework better understanding ecological evolutionary roles microbiome.

Язык: Английский

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Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 25, 2024

Abstract Amino acid availability is monitored by animals to adapt their nutritional environment. Beyond gustatory receptors and systemic amino sensors, enteroendocrine cells (EECs) are believed directly percept dietary acids secrete regulatory peptides. However, the cellular machinery underlying acid-sensing EECs how EEC-derived hormones modulate feeding behavior remain elusive. Here, developing tools specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female inhibits feeding, similar human PYY. Mechanistically, L-Glutamate acts through metabotropic glutamate receptor mGluR decelerate calcium oscillations in thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive relay an anorexigenic signal brain. Thus, our findings provide mechanistic insights into assess food quality identify a conserved mode of action explains gut NPF/PYY modulates intake.

Язык: Английский

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A single-cell atlas of the Culex tarsalis midgut during West Nile virus infection

PLoS Pathogens, Год журнала: 2025, Номер 21(1), С. e1012855 - e1012855

Опубликована: Янв. 27, 2025

The mosquito midgut functions as a key interface between pathogen and vector. However, studies of physiology virus infection dynamics are scarce, in Culex tarsalis— an extremely efficient vector West Nile (WNV) — nonexistent. We performed single-cell RNA sequencing on Cx. tarsalis midguts, defined multiple cell types, determined whether specific types more permissive to WNV infection. identified 20 states comprising 8 distinct consistent with existing descriptions Drosophila Aedes aegypti physiology. Most populations were there higher levels (vRNA) enteroendocrine cells, suggesting enhanced replication this population. In contrast, proliferating intestinal stem cells (ISC) had the lowest vRNA, finding ISC proliferation is involved control. ISCs also found have strong transcriptional response infection; genes ribosome structure biogenesis, translation significantly downregulated WNV-infected populations. Notably, we did not detect significant WNV-infection induced upregulation canonical antiviral immune (e.g., AGO2 , R2D2 etc.) at whole-midgut level. Rather, observed positive correlation gene expression vRNA load individual that within high may trigger responses. Our findings establish atlas, provide insight into by characterizing cell-type enhancement/restriction of, to,

Язык: Английский

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Drosophila AHR limits tumor growth and stem cell proliferation in the intestine

Wellcome Open Research, Год журнала: 2025, Номер 10, С. 38 - 38

Опубликована: Фев. 3, 2025

Background The aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation the epithelium. Spineless, Drosophila homolog of AHR, has only been studied context development but not adult intestine. Methods role Spineless midgut was by overexpression or knockdown infection models RNA sequencing sorted progenitor cells. Results We show that spineless is upregulated epithelium after with Pseudomonas entomophila (P.e.). increased stem cell proliferation following infection-induced injury. limited reduced survival infection. In two models, using either Notch RNAi constitutively active Yorkie, suppressed doubled lifespan tumour-bearing flies. At transcriptional level it reversed gene expression changes induced Yorkie tumours, counteracting altered metabolism. Conclusions These findings demonstrate a new for highlight evolutionarily conserved functions AHR/Spineless control epithelium.

Язык: Английский

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Oral administration of aripiprazole to Drosophila causes intestinal toxicity

Disease Models & Mechanisms, Год журнала: 2025, Номер 18(3)

Опубликована: Март 1, 2025

ABSTRACT Aripiprazole is a third-generation antipsychotic medication that was introduced to mitigate the poor tolerability of older antipsychotics. In contrast drugs act as dopamine receptor antagonists in brain, aripiprazole functions partial agonist. has been identified an off-target inhibitor mitochondrial respiratory complex I. We observed patients prescribed often report gastrointestinal disturbances, but mechanism underlying these side effects not clear. modelled potential toxicity system using fruit fly (Drosophila melanogaster). consumption impaired Drosophila gut function and faecal output. It also reduced membrane increased reactive oxygen species (ROS) levels intestinal cells. ROS activate c-Jun N-terminal kinase (JNK) pathway, which induces cellular stress cell death. JNK activation cells flies, resulting death, suppressed by antioxidants. conclude activates pathway death via production. Using antioxidant supplements may help reduce aripiprazole-induced toxicity.

Язык: Английский

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