Ursodeoxycholic Acid Inhibits Liver X Receptor alpha-mediated Hepatic Lipogenesis via Induction of the Nuclear Corepressor SMILE
DC Field | Value | Language |
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dc.contributor.author | Lee, Ji-Min | - |
dc.contributor.author | Gang, Gil-Tae | - |
dc.contributor.author | Kim, Don-Kyu | - |
dc.contributor.author | Kim, Yong Deuk | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.contributor.author | Lee, Chul-Ho | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.date.accessioned | 2021-09-05T12:22:20Z | - |
dc.date.available | 2021-09-05T12:22:20Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-01-10 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/99546 | - |
dc.description.abstract | Small heterodimer partner interacting leucine zipper protein (SMILE) has been identified as a nuclear corepressor of the nuclear receptor (NRs) family. Here, we examined the role of SMILE in the regulation of nuclear receptor liver X receptor (LXR alpha)-mediated sterol regulatory element binding protein-1c (SREBP-1c) gene expression. We found that SMILE inhibited T0901317 (T7)-induced transcriptional activity of LXR alpha, which functions as a major regulator of lipid metabolism by inducing SREBP-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) gene expression. Moreover, we demonstrated that SMILE physically interacts with LXR alpha and represses T7-induced LXR alpha transcriptional activity by competing with coactivator SRC-1. Adenoviral overexpression of SMILE (Ad-SMILE) attenuated fat accumulation and lipogenic gene induction in the liver of T7 administered or of high fat diet (HFD)-fed mice. Furthermore, we investigated the mechanism by which ursodeoxycholic acid (UDCA) inhibits LXR alpha-induced lipogenic gene expression. Interestingly, UDCA treatment significantly increased SMILE promoter activity and gene expression in an adenosine monophosphate-activated kinase-dependent manner. Furthermore, UDCA treatment repressed T7-induced SREBP-1c, FAS, and ACC protein levels, whereas knockdown of endogenous SMILE gene expression by adenovirus SMILE shRNA (Ad-shSMILE) significantly reversed UDCA-mediated repression of SREBP-1c, FAS, and ACC protein levels. Collectively, these results demonstrate that UDCA activates SMILE gene expression through adenosine monophosphate-activated kinase phosphorylation, which leads to repression of LXR alpha-mediated hepatic lipogenic enzyme gene expression. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | BILE-ACIDS | - |
dc.subject | LXR-ALPHA | - |
dc.subject | CHENODEOXYCHOLIC ACID | - |
dc.subject | BINDING PROTEIN | - |
dc.subject | ACTIVATION | - |
dc.subject | TRANSCRIPTION | - |
dc.subject | HETERODIMER | - |
dc.subject | INTERACTS | - |
dc.subject | PATHWAY | - |
dc.subject | ELEMENT | - |
dc.title | Ursodeoxycholic Acid Inhibits Liver X Receptor alpha-mediated Hepatic Lipogenesis via Induction of the Nuclear Corepressor SMILE | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koo, Seung-Hoi | - |
dc.identifier.doi | 10.1074/jbc.M113.491522 | - |
dc.identifier.scopusid | 2-s2.0-84891909092 | - |
dc.identifier.wosid | 000330541200040 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.289, no.2, pp.1079 - 1091 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.title | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.volume | 289 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 1079 | - |
dc.citation.endPage | 1091 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | BILE-ACIDS | - |
dc.subject.keywordPlus | LXR-ALPHA | - |
dc.subject.keywordPlus | CHENODEOXYCHOLIC ACID | - |
dc.subject.keywordPlus | BINDING PROTEIN | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.subject.keywordPlus | HETERODIMER | - |
dc.subject.keywordPlus | INTERACTS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | ELEMENT | - |
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