B细胞来源的伤害肽/孤啡肽FQ有助于肥胖患者的葡萄糖耐量受损和胰岛素抵抗

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-04 DOI:10.1016/j.isci.2025.112819

Stephanie C. Puente-Ruiz , Leona Ide , Julia Schuller , Adel Ben-Kraiem , Anne Hoffmann , Adhideb Ghosh , Falko Noé , Christian Wolfrum , Kerstin Krause , Martin Gericke , Nora Klöting , Jens C. Brüning , F. Thomas Wunderlich , Matthias Blüher , Alexander Jais

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引用次数: 0

摘要

免疫衍生的阿片肽与免疫调节和炎症过程有关。在这里，我们研究了nociceptin/orphanin FQ （N/OFQ）对肥胖代谢功能和炎症的影响。B细胞选择性靶向Pnoc基因编码的N/OFQ，可减轻饮食引起的肥胖的不良代谢影响，增强胰岛素敏感性和葡萄糖耐量。值得注意的是，B细胞特异性Pnoc敲除小鼠在脂肪组织和肝脏中显示免疫细胞迁移标记物和巨噬细胞募集减少。在机制上，我们发现N/OFQ促进巨噬细胞募集和代谢性炎症，加剧肥胖期间的葡萄糖耐受不良和胰岛素抵抗。总的来说，N/OFQ-NOP系统所表现出的免疫调节特性使其成为减轻代谢性炎症的有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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

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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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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