Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, S.W. | - |
dc.contributor.author | Oh, H. | - |
dc.contributor.author | Park, S.Y. | - |
dc.contributor.author | Cho, W. | - |
dc.contributor.author | Abd, El-Aty A.M. | - |
dc.contributor.author | Baygutalp, N.K. | - |
dc.contributor.author | Jeong, J.H. | - |
dc.contributor.author | Jung, T.W. | - |
dc.date.accessioned | 2024-01-09T14:05:03Z | - |
dc.date.available | 2024-01-09T14:05:03Z | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.issn | 1879-0631 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/70346 | - |
dc.description.abstract | Aims: The current study investigated whether netrin-1 can attenuate hepatic steatosis through PPARγ/autophagy-mediated suppression of inflammation and endoplasmic reticulum (ER) stress in experimental animal models. Main methods: Hepatic steatosis was induced by a high-fat diet in experimental mice. Recombinant mouse netrin-1 was administered via the tail vein (1 μg/mouse, once every two days). Serum inflammatory cytokines and hepatic inflammatory and ER stress markers were determined in mice using ELISA and western blotting protocol. Key findings: We found that netrin-1 expression was significantly increased (P < 0.05) in cultured macrophages treated with supernatants of subcutaneous adipocytes in the presence of palmitate and subcutaneous fat of obese mice. Recombinant netrin-1 treatment promoted PPARγ expression and autophagy, thereby attenuating inflammation and ER stress, lipid accumulation, and the expression of lipogenic proteins in mouse primary hepatocytes. High-fat diet (HFD) treatment increased hepatic inflammation and ER stress, causing hepatic steatosis in experimental mice. However, administration of netrin-1 reversed the effects of HFD on hepatic ER stress and lipid deposition. Significance: These results suggest that subcutaneous adipose macrophage-derived netrin-1 ameliorates inflammation and ER stress in the liver, which in turn alleviates hepatic steatosis by enhancing basal PPARγ/autophagy-dependent signaling. The current study sheds light on the pathogenesis of hepatic steatosis in obesity and provides a promising therapeutic approach for treating metabolic-associated fatty liver disease (MAFLD). © 2022 Elsevier Inc. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Elsevier Inc. | - |
dc.title | Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.lfs.2022.121149 | - |
dc.identifier.bibliographicCitation | Life Sciences, v.311 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000954467600004 | - |
dc.identifier.scopusid | 2-s2.0-85142180041 | - |
dc.citation.title | Life Sciences | - |
dc.citation.volume | 311 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | Autophagy | - |
dc.subject.keywordAuthor | ER stress | - |
dc.subject.keywordAuthor | Inflammation | - |
dc.subject.keywordAuthor | Metabolic-associated fatty liver disease | - |
dc.subject.keywordAuthor | Netrin-1 | - |
dc.subject.keywordAuthor | PPARγ | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | ACTIVATED RECEPTOR-GAMMA | - |
dc.subject.keywordPlus | UNC5B RECEPTOR | - |
dc.subject.keywordPlus | PPAR-GAMMA | - |
dc.subject.keywordPlus | INJURY | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | ISCHEMIA | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | OBESITY | - |
dc.subject.keywordPlus | BRAIN | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.