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Puente-Ruiz, S.C. ; Ide, L. ; Schuller, J. ; Ben-Kraiem, A. ; Hoffmann, A. ; Ghosh, A.* ; Noé, F.* ; Wolfrum, C.* ; Krause, K.* ; Gericke, M.* ; Klöting, N. ; Brüning, J.C.* ; Wunderlich, F.T.* ; Blüher, M. ; Jais, A.

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

iScience 28:112819 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Immune-derived opioid peptides have been implicated in immune regulation and inflammatory processes. Here, we investigate the effects of nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in obesity. Selectively targeting N/OFQ, encoded by the Pnoc gene, in B cells mitigates the adverse metabolic effects of diet-induced obesity and enhances insulin sensitivity and glucose tolerance. Notably, B cell-specific Pnoc knockout mice display a marked reduction in markers of immune cell migration and diminished macrophage recruitment in adipose tissue and liver. Mechanistically, we identify that N/OFQ promotes macrophage recruitment and metabolic inflammation, exacerbating glucose intolerance and insulin resistance during obesity. Overall, the immunomodulatory properties exhibited by the N/OFQ-NOP system render it a promising therapeutic target for mitigating metabolic inflammation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biological Sciences ; Endocrinology ; Natural Sciences ; Physiology; Receptor Antagonist; Adipose-tissue; Immune Cells; Orphanin-fq; Inflammation; Expression; Lymphocytes; Peptide; Chemotaxis; Inhibition
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 28, Issue: 7, Pages: , Article Number: 112819 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-555600-001
G-506501-001
G-506500-001
Grants Federal government of Saxony, Germany
Helmholtz Center Munich
EFSD/Novo Nordisk Foundation
German Research Foundation (DFG)
DOI 10.1016/j.isci.2025.112819
WOS ID 001521628600003
Scopus ID 105008826394
PubMed ID 40662198
Erfassungsdatum 2025-07-01
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