https://scholars.lib.ntu.edu.tw/handle/123456789/462644
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | KAI-WEN HUANG | en_US |
dc.contributor.author | Reebye V. | en_US |
dc.contributor.author | Czysz K. | en_US |
dc.contributor.author | Ciriello S. | en_US |
dc.contributor.author | Dorman S. | en_US |
dc.contributor.author | Reccia I. | en_US |
dc.contributor.author | HONG-SHIEE LAI | en_US |
dc.contributor.author | Peng L. | en_US |
dc.contributor.author | Kostomitsopoulos N. | en_US |
dc.contributor.author | Nicholls J. | en_US |
dc.contributor.author | Habib R.S. | en_US |
dc.contributor.author | Tomalia D.A. | en_US |
dc.contributor.author | S?trom P. | en_US |
dc.contributor.author | Wilkes E. | en_US |
dc.contributor.author | Cutillas P. | en_US |
dc.contributor.author | Rossi J.J. | en_US |
dc.contributor.author | Habib N.A. | en_US |
dc.creator | Huang K.-W.;Reebye V.;Czysz K.;Ciriello S.;Dorman S.;Reccia I.;Hong-Shiee Lai;Peng L.;Kostomitsopoulos N.;Nicholls J.;Habib R.S.;Tomalia D.A.;S?Trom P.;Wilkes E.;Cutillas P.;Rossi J.J.;Habib N.A. | - |
dc.date.accessioned | 2020-02-25T03:19:37Z | - |
dc.date.available | 2020-02-25T03:19:37Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 2162-2531 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076717809&doi=10.1016%2fj.omtn.2019.10.044&partnerID=40&md5=3b07c55ddd6b914faafe805dea6c7252 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/462644 | - |
dc.description.abstract | Non-alcoholic fatty liver disease (NAFLD) culminates in insulin resistance and metabolic syndrome. Because there are no approved pharmacological treatment agents for non-alcoholic steatohepatitis (NASH) and NAFLD, different signaling pathways are under investigation for drug development with the focus on metabolic pathways. Hepatocyte nuclear factor 4-alpha (HNF4A) is at the center of a complex transcriptional network where its disruption is directly linked to glucose and lipid metabolism. Resetting HNF4A expression in NAFLD is therefore crucial for re-establishing normal liver function. Here, small activating RNA (saRNA) specific for upregulating HNF4A was injected into rats fed a high-fat diet for 16 weeks. Intravenous delivery was carried out using 5-(G5)-triethanolamine-core polyamidoamine (PAMAM) dendrimers. We observed a significant reduction in liver triglyceride, increased high-density lipoprotein/low-density lipoprotein (HDL/LDL) ratio, and decreased white adipose tissue/body weight ratio, all parameters to suggest that HNF4A-saRNA treatment induced a favorable metabolic profile. Proteomic analysis showed significant regulation of genes involved in sphingolipid metabolism, fatty acid β-oxidation, ketogenesis, detoxification of reactive oxygen species, and lipid transport. We demonstrate that HNF4A activation by oligonucleotide therapy may represent a novel single agent for the treatment of NAFLD and insulin resistance. ? 2019 The Author(s) | - |
dc.publisher | Cell Press | - |
dc.relation.ispartof | Molecular Therapy - Nucleic Acids | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | albumin; cyclic AMP dependent protein kinase regulatory subunit Ialpha; cyclic AMP dependent protein kinase regulatory subunit Ibeta; cyclic AMP responsive element binding protein; cytochrome P450 3A4; cytochrome P450 3A5; cytochrome P450 3A7; dendrimer; glycogen synthase kinase 3beta; heat shock protein 90; hepatocyte nuclear factor 4alpha; high density lipoprotein; interleukin 6; low density lipoprotein; messenger RNA; polyamidoamine; protein Cdc42; reactive oxygen metabolite; rifampicin; RNA; small activating RNA; triacylglycerol; triethanolamine; unclassified drug; animal experiment; animal model; animal tissue; Article; body weight; controlled study; dyslipidemia; glucose metabolism; glucose transport; Hep-G2 cell line; hippo signaling; human; human cell; insulin resistance; ketogenesis; lipid blood level; lipid diet; lipid metabolism; lipid transport; liver histology; male; nonalcoholic fatty liver; nonhuman; oligonucleotide therapy; priority journal; protein expression; protein protein interaction; proteomics; rat; real time polymerase chain reaction; sphingolipid metabolism; upregulation; Western blotting; white adipose tissue | - |
dc.title | Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1016/j.omtn.2019.10.044 | - |
dc.identifier.scopus | 2-s2.0-85076717809 | - |
dc.relation.pages | 361-370 | - |
dc.relation.journalvolume | 19 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.orcid | 0000-0001-6375-8714 | - |
crisitem.author.orcid | 0000-0002-7958-2183 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學系 |
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