Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity [liver]

ABSTRACT: B cells play a significant, yet underexplored, role in modulating immune responses in obesity and type 2 diabetes. In this study, we investigate the impact of B cell-derived nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in the context of obesity. Using a B cell-specific Pnoc knockout mouse model (PnocΔCD19), we demonstrate that loss of N/OFQ expression in B cells improves insulin sensitivity and glucose tolerance, particularly in the context of high-fat diet (HFD)-induced obesity. PnocΔCD19 mice exhibit a marked reduction in immune cell migration markers and macrophage recruitment in liver and adipose tissue. Mechanistically, we demonstrate that N/OFQ facilitates macrophage migration, contributing to the glucose intolerance and insulin resistance associated with obesity. Overall, the immunomodulatory properties exhibited by the N/OFQ-NOP system render it a compelling therapeutic target for metabolic inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE281911 | GEO | 2025/05/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity

Project description:B cells play a significant, yet underexplored, role in modulating immune responses in obesity and type 2 diabetes. In this study, we investigate the impact of B cell-derived nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in the context of obesity. Using a B cell-specific Pnoc knockout mouse model (PnocΔCD19), we demonstrate that loss of N/OFQ expression in B cells improves insulin sensitivity and glucose tolerance, particularly in the context of high-fat diet (HFD)-induced obesity. PnocΔCD19 mice exhibit a marked reduction in immune cell migration markers and macrophage recruitment in liver and adipose tissue. Mechanistically, we demonstrate that N/OFQ facilitates macrophage migration, contributing to the glucose intolerance and insulin resistance associated with obesity. Overall, the immunomodulatory properties exhibited by the N/OFQ-NOP system render it a compelling therapeutic target for metabolic inflammation.

2025-05-12 | GSE281815 | GEO

B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity [THP1]

2025-05-12 | GSE281913 | GEO

Nociceptin/orphanin FQ opioid receptor selective ligand MCOPPB as a potent senolytic drug

Project description:Nociceptin/orphanin FQ opioid receptor selective ligand MCOPPB as a potent senolytic drug

| PRJNA678239 | ENA

Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists

Project description:Agonists for the nociceptin/orphanin FQ opioid peptide NOP receptor, a member of the opioid receptor family, are under active investigation as novel analgesics, but their modes of signaling are less well characterized than those for other members of the opioid receptor family. Therefore, we investigated whether different NOP receptor ligands show differential signaling or functional selectivity at the NOP receptor. Using newly developed phosphosite-specific antibodies to NOP receptor, we found that agonist-induced NOP receptor phosphorylation occurred primarily at four carboxyl-terminal serine (S) and threonine (T) residues, namely Ser346, Ser351, Thr362 and Ser363, and proceeded with a temporal hierarchy, with Ser346 as the first site of phosphorylation. G protein-coupled receptor kinases 2 and 3 (GRK2/3) cooperated during agonist-induced phosphorylation, which in turn facilitated NOP receptor desensitization and internalization. A comparison of structurally distinct NOP receptor agonists revealed dissociation in functional efficacies between G protein-dependent signaling and receptor phosphorylation. Furthermore, in vivo, in NOP-eGFP and NOP-eYFP mice, NOP receptor agonists induced multisite phosphorylation and internalization in a dose-dependent and agonist-selective manner that could be blocked by specific antagonists. Together, our study provides novel tools to study ligand-activated NOP receptor signaling in vitro and in vivo. Differential agonist-selective NOP receptor phosphorylation by chemically diverse NOP receptor agonists suggests that differential signaling by NOP receptor agonists may play a role in NOP receptor ligand pharmacology.

2020-05-26 | PXD012908 | Pride

RiboTag enrichment of aBNST nociceptin neurons

Project description:We report the differential expression of genes in aBNST nociceptin neurons in comparison to the whole aBNST in mice

2019-11-04 | GSE135982 | GEO

RiboTag enrichment of aBNST nociceptin neurons

Project description:RiboTag enrichment of aBNST nociceptin neurons

| PRJNA560879 | ENA

Hypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis

Project description:We show that leptin regulates appetite and body weight via PNOC neurons, and that loss of leptin receptor expression in PNOC-expressing neurons in the arcuate nucleus of the hypothalamus (ARC) causes hyperphagia and obesity. Lepr inactivation in PNOC neurons increases Npy expression in a subset of hypothalamic PNOC neurons that do not express Agrp and selective chemogenetic activation of PNOC/NPY neurons promotes feeding to the same extent as activating all PNOCARC neurons and overexpression of Npy in PNOCARC neurons promotes hyperphagia and obesity. Thus, we introduce PNOC/NPYARC neurons as an additional critical mediator of leptin action and a promising target for obesity therapeutics.

2025-04-23 | GSE292416 | GEO

Aliivibrio fischeri strain:FQ-A001

Project description:Aliivibrio fischeri strain:FQ-A001 Genome sequencing and assembly

| PRJNA524701 | ENA

Nociceptin/orphanin FQ receptor agonists attenuate L-DOPA-induced dyskinesias.

Project description:In the present study we investigated whether the neuropeptide nociceptin/orphanin FQ (N/OFQ), previously implicated in the pathogenesis of Parkinson's disease, also affects L-DOPA-induced dyskinesia. In striatal slices of naive rodents, N/OFQ (0.1-1 ?m) prevented the increase of ERK phosphorylation and the loss of depotentiation of synaptic plasticity induced by the D1 receptor agonist SKF38393 in spiny neurons. In vivo, exogenous N/OFQ (0.03-1 nmol, i.c.v.) or a synthetic N/OFQ receptor agonist given systemically (0.01-1 mg/Kg) attenuated dyskinesias expression in 6-hydroxydopamine hemilesioned rats primed with L-DOPA, without causing primary hypolocomotive effects. Conversely, N/OFQ receptor antagonists worsened dyskinesia expression. In vivo microdialysis revealed that N/OFQ prevented dyskinesias simultaneously with its neurochemical correlates such as the surge of nigral GABA and glutamate, and the reduction of thalamic GABA. Regional microinjections revealed that N/OFQ attenuated dyskinesias more potently and effectively when microinjected in striatum than substantia nigra (SN) reticulata, whereas N/OFQ receptor antagonists were ineffective in striatum but worsened dyskinesias when given in SN. Quantitative autoradiography showed an increase in N/OFQ receptor binding in striatum and a reduction in SN of both unprimed and dyskinetic 6-hydroxydopamine rats, consistent with opposite adaptive changes of N/OFQ transmission. Finally, the N/OFQ receptor synthetic agonist also reduced dyskinesia expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated dyskinetic macaques without affecting the global parkinsonian score. We conclude that N/OFQ receptor agonists may represent a novel strategy to counteract L-DOPA-induced dyskinesias. Their action is possibly mediated by upregulated striatal N/OFQ receptors opposing the D1 receptor-mediated overactivation of the striatonigral direct pathway.

| S-EPMC6794016 | biostudies-literature

Structure- and conformation-activity studies of nociceptin/orphanin FQ receptor dimeric ligands.

Project description:The peptide nociceptin/orphanin FQ (N/OFQ) and the N/OFQ receptor (NOP) constitute a neuropeptidergic system that modulates various biological functions and is currently targeted for the generation of innovative drugs. In the present study dimeric NOP receptor ligands with spacers of different lengths were generated using both peptide and non-peptide pharmacophores. The novel compounds (12 peptide and 7 nonpeptide ligands) were pharmacologically investigated in a calcium mobilization assay and in the mouse vas deferens bioassay. Both structure- and conformation-activity studies were performed. Results demonstrated that dimerization did not modify the pharmacological activity of both peptide and non-peptide pharmacophores. Moreover, when dimeric compounds were obtained with low potency peptide pharmacophores, dimerization recovered ligand potency. This effect depends on the doubling of the C-terminal address sequence rather than the presence of an additional N-terminal message sequence or modifications of peptide conformation.

| S-EPMC5382891 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data