6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 Cascade
DC Field | Value | Language |
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dc.contributor.author | Ahn, Jiyun | - |
dc.contributor.author | Lee, Hyunjung | - |
dc.contributor.author | Jung, Chang Hwa | - |
dc.contributor.author | Ha, Seung Yeon | - |
dc.contributor.author | Seo, Hyo-Deok | - |
dc.contributor.author | Kim, Young In | - |
dc.contributor.author | Ha, Taeyoul | - |
dc.date.accessioned | 2021-11-05T01:40:42Z | - |
dc.date.available | 2021-11-05T01:40:42Z | - |
dc.date.created | 2021-09-20 | - |
dc.date.issued | 2021-01 | - |
dc.identifier.issn | 2352-345X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82602 | - |
dc.description.abstract | Background & Aims: The development of nonalcoholic fatty liver disease (NAFLD) can be modulated by microRNAs (miRNA). Dietary polyphenols modulate the expression of miRNA such as miR-467b-3p in the liver. In addition, 6-gingerol (6-G), the functional polyphenol of ginger, has been reported to ameliorate hepatic steatosis; however, the exact mechanism involved and the role of miRNA remain elusive. In this study, we assessed the role of miR-467b-3p in the pathogenesis of hepatic steatosis and the regulation of miR-467b-3p by 6-G through the hepatocyte nuclear factor 4α (HNF4α). Methods: miR-467b-3p expression was measured in free fatty acid (FFA)-treated hepatocytes or liver from high-fat diet (HFD)-fed mice. Gain- or loss-of-function of miR-467b-3p was induced using miR-467b-3p–specific miRNA mimic or miRNA inhibitor, respectively. 6-G was exposed to FFA-treated cells and HFD-fed mice. The HNF4α/miR-467b-3p/GPAT1 axis was measured in mouse and human fatty liver tissues. Results: We found that miR-467b-3p was down-regulated in liver tissues from HFD-fed mice and in FFA-treated Hepa1-6 cells. Overexpression of miR-467b-3p decreased intracellular lipid accumulation in FFA-treated hepatocytes and mitigated hepatic steatosis in HFD-fed mice via negative regulation of glycerol-3-phosphate acyltransferase-1 (GPAT1). In addition, miR-467b-3p up-regulation by 6-G was observed. 6-G inhibited FFA-induced lipid accumulation and mitigated hepatic steatosis. Moreover, it increased the transcriptional activity of HNF4α, resulting in the increase of miR-467b-3p and subsequent decrease of GPAT1. HNF4α/miR-467b-3p/GPAT1 signaling also was observed in human samples with hepatic steatosis. Conclusions: Our findings establish a novel mechanism by which 6-G improves NAFLD. This suggests that targeting of the HNF4α/miR-467b-3p/GPAT1 cascade may be used as a potential therapeutic strategy to control NAFLD. © 2021 The Authors | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER INC | - |
dc.relation.isPartOf | Cellular and Molecular Gastroenterology and Hepatology | - |
dc.title | 6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 Cascade | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000709680200002 | - |
dc.identifier.doi | 10.1016/j.jcmgh.2021.06.007 | - |
dc.identifier.bibliographicCitation | Cellular and Molecular Gastroenterology and Hepatology, v.12, no.4, pp.1201 - 1213 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85114821550 | - |
dc.citation.endPage | 1213 | - |
dc.citation.startPage | 1201 | - |
dc.citation.title | Cellular and Molecular Gastroenterology and Hepatology | - |
dc.citation.volume | 12 | - |
dc.citation.number | 4 | - |
dc.contributor.affiliatedAuthor | Ha, Seung Yeon | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | 6-gingerol | - |
dc.subject.keywordAuthor | GPAT1 | - |
dc.subject.keywordAuthor | HNF4α | - |
dc.subject.keywordAuthor | MicroRNA | - |
dc.subject.keywordAuthor | NAFLD | - |
dc.subject.keywordPlus | FATTY-ACID OXIDATION | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | DIET | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | MICRORNAS | - |
dc.subject.keywordPlus | GINGER | - |
dc.subject.keywordPlus | MICE | - |
dc.relation.journalResearchArea | Gastroenterology & Hepatology | - |
dc.relation.journalWebOfScienceCategory | Gastroenterology & Hepatology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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