• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

鉴定神经突蛋白1作为棕色脂肪组织的局部代谢调节因子。

Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue.

作者信息

Sánchez-Feutrie Manuela, Romero Montserrat, Veiga Sónia R, Borràs-Ferré Núria, Berrow Nick, Ràfols Martina, Giménez Noemí, Rodgers-Furones Andrea, Sabaté-Pérez Alba, Rodríguez Pérez Ángela, Cataldo Luis Rodrigo, Burghardt Hans, Sebastián David, Plana Natàlia, Hernández Vanessa, Alcaide Laura Isabel, Reina Óscar, Monte Maria J, Marin José Juan G, Palacín Manuel, Burcelin Remy, Antonson Per, Gustafsson Jan-Ake, Zorzano Antonio

机构信息

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.

Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028, Barcelona, Spain.

出版信息

Nat Commun. 2025 Sep 4;16(1):7033. doi: 10.1038/s41467-025-62255-2.

DOI:
10.1038/s41467-025-62255-2
PMID:40908286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12411623/
Abstract

Brown adipose tissue (BAT) plays a key role in metabolic homeostasis through its thermogenic effects and the secretion of regulatory molecules. Here we report that RAP250 haploinsufficiency stimulates BAT in mice, thus contributing to a decrease in fat accumulation. Local in vivo AAV-mediated RAP250 silencing in BAT reduces body weight and fat mass and enhances glucose oxidation, thereby indicating that RAP250 participates in the regulation of BAT metabolic activity. Analysis of the mechanisms led to the finding that Neuritin 1 is produced and released by brown adipocytes, it plays a key metabolic role, and it participates in the enhanced BAT metabolic activity under RAP250 deficiency. Forced overexpression of Neuritin 1 in UCP1-expressing cells markedly decreases fat mass and body weight gain in mice and induces the expression of thermogenic genes in BAT. Neuritin 1-deficient brown adipocytes also shows a reduced β-adrenergic response. We demonstrate a metabolic role of BAT-derived Neuritin 1 acting through an autocrine/paracrine mechanism. Based on our results, Neuritin-1 emerges as a potential target for the treatment of metabolic disorders.

摘要

棕色脂肪组织（BAT）通过其产热作用和调节分子的分泌在代谢稳态中发挥关键作用。在此，我们报告RAP250单倍体不足会刺激小鼠的棕色脂肪组织，从而有助于减少脂肪堆积。在棕色脂肪组织中通过局部体内腺相关病毒介导的RAP250沉默可降低体重和脂肪量，并增强葡萄糖氧化，从而表明RAP250参与棕色脂肪组织代谢活性的调节。对机制的分析发现，神经生长因子1由棕色脂肪细胞产生并释放，它发挥关键的代谢作用，并参与RAP250缺乏时棕色脂肪组织代谢活性的增强。在表达解偶联蛋白1（UCP1）的细胞中强制过表达神经生长因子1可显著降低小鼠的脂肪量和体重增加，并诱导棕色脂肪组织中产热基因的表达。缺乏神经生长因子1的棕色脂肪细胞也表现出β-肾上腺素能反应降低。我们证明了棕色脂肪组织来源的神经生长因子1通过自分泌/旁分泌机制发挥代谢作用。基于我们的研究结果，神经生长因子1成为治疗代谢紊乱的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/37812eda8cd8/41467_2025_62255_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/31ef2fe03ce3/41467_2025_62255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/c049bc02b48e/41467_2025_62255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/acdf5084561b/41467_2025_62255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/610b46350281/41467_2025_62255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/6600ff6b1c18/41467_2025_62255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/8f7cd0b16913/41467_2025_62255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/2d85c46e2eb4/41467_2025_62255_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/37812eda8cd8/41467_2025_62255_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/31ef2fe03ce3/41467_2025_62255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/c049bc02b48e/41467_2025_62255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/acdf5084561b/41467_2025_62255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/610b46350281/41467_2025_62255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/6600ff6b1c18/41467_2025_62255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/8f7cd0b16913/41467_2025_62255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/2d85c46e2eb4/41467_2025_62255_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbaf/12411623/37812eda8cd8/41467_2025_62255_Fig8_HTML.jpg

相似文献

1
Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue.鉴定神经突蛋白1作为棕色脂肪组织的局部代谢调节因子。
Nat Commun. 2025 Sep 4;16(1):7033. doi: 10.1038/s41467-025-62255-2.
2
Ablation of FAM210A in Brown Adipocytes of Mice Exacerbates High-Fat Diet-Induced Metabolic Dysfunction.小鼠棕色脂肪细胞中FAM210A的缺失加剧了高脂饮食诱导的代谢功能障碍。
Diabetes. 2025 Mar 1;74(3):282-294. doi: 10.2337/db24-0294.
3
Mitochondrial ATP-sensitive K channels (MitoK) regulate brown adipocyte differentiation and metabolism.线粒体ATP敏感性钾通道（MitoK）调节棕色脂肪细胞的分化和代谢。
Am J Physiol Cell Physiol. 2025 Aug 1;329(2):C574-C584. doi: 10.1152/ajpcell.00070.2025. Epub 2025 Jul 11.
4
Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets.肌红蛋白在小鼠的棕色脂肪组织中表达，调节线粒体和脂滴的含量和活性。
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Dec;1866(12):159026. doi: 10.1016/j.bbalip.2021.159026. Epub 2021 Aug 10.
5
Bidirectional shifts in Pm20d1 expression impact thermogenesis and metabolism.Pm20d1表达的双向变化影响产热和新陈代谢。
Mol Med. 2025 Aug 28;31(1):283. doi: 10.1186/s10020-025-01345-9.
6
Guanosine enhances thermogenesis and impairs KEAP1-mediated NRF2 degradation to resist ferroptosis in brown adipose tissue.鸟苷增强产热并损害KEAP1介导的NRF2降解，以抵抗棕色脂肪组织中的铁死亡。
Free Radic Biol Med. 2025 Oct;238:360-369. doi: 10.1016/j.freeradbiomed.2025.07.003. Epub 2025 Jul 3.
7
The Mitochondrial Brown Adipose Tissue Maintenance Factor Nipsnap1 Interfaces Directly With the β-Oxidation Protein Machinery in Rodents.线粒体棕色脂肪组织维持因子Nipsnap1与啮齿动物的β-氧化蛋白机制直接相互作用。
J Nutr. 2025 Jul;155(7):2154-2163. doi: 10.1016/j.tjnut.2025.05.026. Epub 2025 May 23.
8
The TBLR1/TBL1 Co-Factor Complex Acts as a Transcriptional Checkpoint in the Brown Adipose Tissue Response to Prolonged Cold Exposure.TBLR1/TBL1辅助因子复合物在棕色脂肪组织对长期寒冷暴露的反应中作为转录检查点发挥作用。
FASEB J. 2025 Aug 15;39(15):e70886. doi: 10.1096/fj.202402993RRR.
9
The Purinergic Receptor P2X5 Modulates Glucose Metabolism and Expression of Thermogenic Genes in Brown Adipose Tissue.嘌呤能受体P2X5调节棕色脂肪组织中的葡萄糖代谢和产热基因表达。
Int J Mol Sci. 2025 Jul 4;26(13):6474. doi: 10.3390/ijms26136474.
10
SENP2 regulates UCP1-dependent thermogenesis in brown adipocytes via deSUMOylation of ERRα.SENP2通过ERRα的去SUMO化作用调节棕色脂肪细胞中UCP1依赖的产热作用。
Exp Mol Med. 2025 Jun;57(6):1283-1293. doi: 10.1038/s12276-025-01458-5. Epub 2025 Jun 27.

本文引用的文献

1
Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity.神经营养因子神经黏附素调节 T 细胞的电和代谢状态，以平衡耐受和免疫。
Elife. 2024 Nov 20;13:RP96812. doi: 10.7554/eLife.96812.
2
Roastgsa: a comparison of rotation-based scores for gene set enrichment analysis.Roastgsa：基于旋转的基因集富集分析评分比较。
BMC Bioinformatics. 2023 Oct 30;24(1):408. doi: 10.1186/s12859-023-05510-x.
3
The nervous system and adipose tissues: a tale of dialogues.神经系统与脂肪组织：对话的故事
Am J Physiol Endocrinol Metab. 2023 Nov 1;325(5):E480-E490. doi: 10.1152/ajpendo.00115.2023. Epub 2023 Sep 20.
4
The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits.2 型糖尿病知识库：一个开放获取的遗传资源库，专门用于 2 型糖尿病和相关特征。
Cell Metab. 2023 Apr 4;35(4):695-710.e6. doi: 10.1016/j.cmet.2023.03.001. Epub 2023 Mar 23.
5
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis.自噬介导的 NCOR1 降解对于棕色脂肪成熟和产热是必需的。
Autophagy. 2023 Mar;19(3):904-925. doi: 10.1080/15548627.2022.2111081. Epub 2022 Aug 25.
6
Regulation of Hepatic Gluconeogenesis by Nuclear Receptor Coactivator 6.核受体共激活因子 6 对肝糖异生的调控
Mol Cells. 2022 Apr 30;45(4):180-192. doi: 10.14348/molcells.2022.2222.
7
The Heartwarming Effect of Brown Adipose Tissue.棕色脂肪组织的暖心效应。
Mol Pharmacol. 2022 Jul;102(1):460-471. doi: 10.1124/molpharm.121.000328. Epub 2021 Dec 21.
8
Vascular smooth muscle-derived Trpv1 progenitors are a source of cold-induced thermogenic adipocytes.血管平滑肌来源的瞬时受体电位香草酸亚型1祖细胞是冷诱导产热脂肪细胞的一个来源。
Nat Metab. 2021 Apr;3(4):485-495. doi: 10.1038/s42255-021-00373-z. Epub 2021 Apr 12.
9
Follicular regulatory T cells produce neuritin to regulate B cells.滤泡调节性 T 细胞产生神经丝蛋白来调节 B 细胞。
Cell. 2021 Apr 1;184(7):1775-1789.e19. doi: 10.1016/j.cell.2021.02.027. Epub 2021 Mar 11.
10
Isolation, Culture, and Functional Analysis of Murine Thermogenic Adipocytes.分离、培养和功能分析小鼠产热脂肪细胞
STAR Protoc. 2020 Sep 22;1(3):100118. doi: 10.1016/j.xpro.2020.100118. eCollection 2020 Dec 18.