The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gwang-Woong | - |
dc.contributor.author | Srivastava, Roshni | - |
dc.contributor.author | Hernandez-Ono, Antonio | - |
dc.contributor.author | Gang, Gyoungok | - |
dc.contributor.author | Smith, Stephen B. | - |
dc.contributor.author | Booth, Carmen J. | - |
dc.contributor.author | Ginsberg, Henry N | - |
dc.contributor.author | Mani, Arya | - |
dc.date.accessioned | 2022-07-16T06:01:29Z | - |
dc.date.available | 2022-07-16T06:01:29Z | - |
dc.date.created | 2021-05-13 | - |
dc.date.issued | 2014-02 | - |
dc.identifier.issn | 1550-4131 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/160621 | - |
dc.description.abstract | The underlying molecular genetic basis of combined hyperlipidemia, the most common atherogenic lipid disorder, is poorly characterized. Rare, nonconservative mutations in the Wnt coreceptor, LRP6, underlie autosomal dominant atherosclerosis, combined hyperlipidemia, and fatty liver disease. Mice with LRP6(R611C) mutation similarly developed elevated plasma LDL and TG levels and fatty liver. Further investigation showed that LRP6(R611C) mutation triggers hepatic de novo lipogenesis, lipid and cholesterol biosynthesis, and apoB secretion by an Sp1-dependent activation of IGF1, AKT, and both mTORC1 and mTORC2. These pathways were normalized after in vitro treatment of primary hepatocytes from LRP6(R611C) mice with either the IGF1R antagonist PPP, rapamycin, or rmWnt3a. Strikingly, in vivo administration of rmWnt3a to LRP6(R611C) mice normalized the altered expression of enzymes of DNL and cholesterol biosynthesis, and restored plasma TG and LDL levels to normal. These findings identify Wnt signaling as a regulator of plasma lipids and a target for treatment of hyperlipidemia. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.title | The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Gwang-Woong | - |
dc.identifier.doi | 10.1016/j.cmet.2013.11.023 | - |
dc.identifier.scopusid | 2-s2.0-84893455140 | - |
dc.identifier.wosid | 000330722600007 | - |
dc.identifier.bibliographicCitation | CELL METABOLISM, v.19, no.2, pp.209 - 220 | - |
dc.relation.isPartOf | CELL METABOLISM | - |
dc.citation.title | CELL METABOLISM | - |
dc.citation.volume | 19 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 209 | - |
dc.citation.endPage | 220 | - |
dc.type.rims | ART | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell BiologyEndocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Cell BiologyEndocrinology & Metabolism | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1550413113004944?via%3Dihub | - |
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