Chemogenetic stimulation of the parasympathetic nervous system lowers hepatic lipid accumulation and inflammation in a nonalcoholic steatohepatitis mouse model
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Hur, Moon Haeng | - |
dc.contributor.author | Song, Woojin | - |
dc.contributor.author | Cheon, Deok-Hyeon | - |
dc.contributor.author | Chang, Young | - |
dc.contributor.author | Cho, Young Youn | - |
dc.contributor.author | Lee, Yun Bin | - |
dc.contributor.author | Yu, Su Jong | - |
dc.contributor.author | Kim, Yoon Jun | - |
dc.contributor.author | Yoon, Jung-Hwan | - |
dc.contributor.author | Choi, Hyung Jin | - |
dc.contributor.author | NamKoong, Cherl | - |
dc.contributor.author | Lee, Jeong-Hoon | - |
dc.date.accessioned | 2023-12-13T03:31:34Z | - |
dc.date.available | 2023-12-13T03:31:34Z | - |
dc.date.issued | 2023-05 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.issn | 1879-0631 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/24746 | - |
dc.description.abstract | Aims: The role of the parasympathetic nervous system (PNS) in the pathogenesis of nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, the effect of PNS modulation on NASH was investigated using chemogenetics. Main methods: A streptozotocin (STZ) and high-fat diet (HFD)-induced NASH mouse model was used. To activate or inhibit the PNS, chemogenetic human M3-muscarinic receptor coupled with either Gq or Gi protein-containing viruses was injected into the dorsal motor nucleus of the vagus at week 4 and clozapine N-oxide was administered intraperitoneally for a week from week 11. Three groups (PNS-stimulation, PNS-inhibition, and control) were compared in terms of heart rate variability (HRV), histological lipid droplet area, nonalcoholic fatty liver disease activity score (NAS), the area of F4/80-positive macrophages, and biochemical responses. Key findings: The STZ/HFD-treated mouse model showed typical histological characteristics of NASH. HRV analysis confirmed that PNS-stimulation and PNS-inhibition groups had significantly higher and lower PNS activity, respectively (both P < 0.05). The PNS-stimulation group showed a significantly smaller hepatic lipid droplet area (14.3 % vs. 20.6 %, P = 0.02) and lower NAS (5.2 vs. 6.3, P = 0.047) than the control group. The area of F4/80-positive macrophages was significantly smaller in the PNS-stimulation group than in the control group (4.1 % vs. 5.6 %, P = 0.04). The PNS-stimulation group showed a lower serum aspartate aminotransferase level than the control group (119.0 vs. 356.0 U/L, P = 0.04). Significance: In STZ/HFD-treated mice, chemogenetic stimulation of the PNS significantly reduced hepatic fat accumulation and inflammation. The hepatic PNS may play a pivotal role in the pathogenesis of NASH. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Elsevier BV | - |
dc.title | Chemogenetic stimulation of the parasympathetic nervous system lowers hepatic lipid accumulation and inflammation in a nonalcoholic steatohepatitis mouse model | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1016/j.lfs.2023.121533 | - |
dc.identifier.scopusid | 2-s2.0-85151483565 | - |
dc.identifier.wosid | 001029190600001 | - |
dc.identifier.bibliographicCitation | Life Sciences, v.321 | - |
dc.citation.title | Life Sciences | - |
dc.citation.volume | 321 | - |
dc.type.docType | Article; Early Access | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | FATTY LIVER-DISEASE | - |
dc.subject.keywordPlus | HEART-RATE-VARIABILITY | - |
dc.subject.keywordPlus | NICOTINIC ACETYLCHOLINE-RECEPTOR | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | SUPPRESSION | - |
dc.subject.keywordPlus | SECRETION | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordAuthor | Brain-liver axis | - |
dc.subject.keywordAuthor | Autonomic nervous system | - |
dc.subject.keywordAuthor | Chemogenetics | - |
dc.subject.keywordAuthor | Fatty liver | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG 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.