Mitochondrial protease ClpP supplementation ameliorates diet- induced NASH in mice
DC Field | Value | Language |
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dc.contributor.author | Choi, Sung -E | - |
dc.contributor.author | Hwang, Yoonjung | - |
dc.contributor.author | Lee, Soo-Jin | - |
dc.contributor.author | Jung, Hyunkyung | - |
dc.contributor.author | Shin, Tae Hwan | - |
dc.contributor.author | Son, Youngho | - |
dc.contributor.author | Park, Seokho | - |
dc.contributor.author | Han, Seung Jin | - |
dc.contributor.author | Kim, Hae Jin | - |
dc.contributor.author | Lee, Kwan Woo | - |
dc.contributor.author | Lee, Gwang | - |
dc.contributor.author | Kemper, Jongsook Kim | - |
dc.contributor.author | Song, Hyun Kyu | - |
dc.contributor.author | Kang, Yup | - |
dc.date.accessioned | 2022-12-09T14:42:20Z | - |
dc.date.available | 2022-12-09T14:42:20Z | - |
dc.date.created | 2022-12-08 | - |
dc.date.issued | 2022-09 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/146609 | - |
dc.description.abstract | Background & Aims: Mitochondrial dysfunction is considered a pathogenic linker in the development of non-alcoholic steato-hepatitis (NASH). Inappropriate mitochondrial protein-quality control, possibly induced by insufficiency of the mitochondrial matrix caseinolytic protease P (ClpP), can potentially cause mitochondrial dysfunction. Herein, we aimed to investigate he-patic ClpP levels in a diet-induced model of NASH and determine whether supplementation of ClpP can ameliorate diet -induced NASH. Methods: NASH was induced by a high-fat/high-fructose (HF/ HFr) diet in C57BL/6J mice. Stress/inflammatory signals were induced in mouse primary hepatocytes (MPHs) by treatment with palmitate/oleate (PA/OA). ClpP levels in hepatocytes were reduced using the RNAi-mediated gene knockdown technique but increased through the viral transduction of ClpP. ClpP acti-vation was induced by administering a chemical activator of ClpP.Results: Hepatic ClpP protein levels in C57BL/6J mice fed a HF/ HFr diet were lower than the levels in those fed a normal chow diet. PA/OA treatment also decreased the ClpP protein levels in MPHs. Overexpression or activation of ClpP reversed PA/OA-induced mitochondrial dysfunction and stress/inflammatory signal activation in MPHs, whereas ClpP knockdown induced mitochondrial dysfunction and stress/inflammatory signals in these cells. On the other hand, ClpP overexpression or activation improved HF/HFr-induced NASH characteristics such as hepatic steatosis, inflammation, fibrosis, and injury in the C57BL/6J mice, whereas ClpP knockdown further augmented steatohepatitis in mice fed a HF/HFr diet.Conclusions: Reduced ClpP expression and subsequent mito-chondrial dysfunction are key to the development of diet -induced NASH. ClpP supplementation through viral trans-duction or chemical activation represents a potential therapeutic strategy to prevent diet-induced NASH.Lay summary: Western diets, containing high fat and high fructose, often induce non-alcoholic steatohepatitis (NASH). Mitochondrial dysfunction is considered pathogenically linked to diet-induced NASH. We observed that the mitochondrial prote-ase ClpP decreased in the livers of mice fed a western diet and supplementation of ClpP ameliorated western diet -induced NASH.(c) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.subject | NONALCOHOLIC FATTY LIVER | - |
dc.subject | INSULIN-RESISTANCE | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | DYSFUNCTION | - |
dc.subject | DISEASE | - |
dc.subject | ADAPTATION | - |
dc.subject | MECHANISMS | - |
dc.subject | PATHWAY | - |
dc.title | Mitochondrial protease ClpP supplementation ameliorates diet- induced NASH in mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Song, Hyun Kyu | - |
dc.identifier.doi | 10.1016/j.jhep.2022.03.034 | - |
dc.identifier.scopusid | 2-s2.0-85131247006 | - |
dc.identifier.wosid | 000885326300018 | - |
dc.identifier.bibliographicCitation | JOURNAL OF HEPATOLOGY, v.77, no.3, pp.735 - 747 | - |
dc.relation.isPartOf | JOURNAL OF HEPATOLOGY | - |
dc.citation.title | JOURNAL OF HEPATOLOGY | - |
dc.citation.volume | 77 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 735 | - |
dc.citation.endPage | 747 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Gastroenterology & Hepatology | - |
dc.relation.journalWebOfScienceCategory | Gastroenterology & Hepatology | - |
dc.subject.keywordPlus | NONALCOHOLIC FATTY LIVER | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | ADAPTATION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordAuthor | inflammation | - |
dc.subject.keywordAuthor | mitochondrial dysfunction | - |
dc.subject.keywordAuthor | proteostasis | - |
dc.subject.keywordAuthor | steatohepatitis | - |
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