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DC Field | Value | Language |
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dc.citation.startPage | e70472 | - |
dc.citation.title | ELIFE | - |
dc.citation.volume | 10 | - |
dc.contributor.author | Lee, Yo Han | - |
dc.contributor.author | Jang, Hyun-Jun | - |
dc.contributor.author | Kim, Sounkou | - |
dc.contributor.author | Choi, Sun Sil | - |
dc.contributor.author | Khim, Keon Woo | - |
dc.contributor.author | Eom, Hye-Jin | - |
dc.contributor.author | Hyun, Jimin | - |
dc.contributor.author | Shin, Kyeong Jin | - |
dc.contributor.author | Chae, Young Chan | - |
dc.contributor.author | Kim, Hongtae | - |
dc.contributor.author | Park, Jiyoung | - |
dc.contributor.author | Park, Neung Hwa | - |
dc.contributor.author | Woo, Chang-Yun | - |
dc.contributor.author | Hong, Chung Hwan | - |
dc.contributor.author | Koh, Eun Hee | - |
dc.contributor.author | Nam, Dougu | - |
dc.contributor.author | Choi, Jang Hyun | - |
dc.date.accessioned | 2023-12-21T14:49:20Z | - |
dc.date.available | 2023-12-21T14:49:20Z | - |
dc.date.created | 2022-01-01 | - |
dc.date.issued | 2021-12 | - |
dc.description.abstract | Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods: Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results: We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions: Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, a |
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dc.identifier.bibliographicCitation | ELIFE, v.10, pp.e70472 | - |
dc.identifier.doi | 10.7554/elife.70472 | - |
dc.identifier.issn | 2050-084X | - |
dc.identifier.scopusid | 2-s2.0-85122031785 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/55897 | - |
dc.identifier.url | https://elifesciences.org/articles/70472 | - |
dc.identifier.wosid | 000746394100001 | - |
dc.language | 영어 | - |
dc.publisher | ELIFE SCIENCES PUBLICATIONS LTD | - |
dc.title | Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA | - |
dc.type | Article | - |
dc.description.isOpenAccess | TRUE | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | miR-20b | - |
dc.subject.keywordAuthor | NAFLD | - |
dc.subject.keywordAuthor | PPAR alpha | - |
dc.subject.keywordAuthor | combination therapy | - |
dc.subject.keywordAuthor | Human | - |
dc.subject.keywordAuthor | Mouse | - |
dc.subject.keywordPlus | LIPID-METABOLISM | - |
dc.subject.keywordPlus | ADIPOSE-TISSUE | - |
dc.subject.keywordPlus | ALPHA | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | STEATOHEPATITIS | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | FIBROSIS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | OBESITY | - |
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