dc.contributor.author | Huang, Kai-Wen | |
dc.contributor.author | Reebye, Vikash | |
dc.contributor.author | Czysz, Katherine | |
dc.contributor.author | Ciriello, Simona | |
dc.contributor.author | Dorman, Stephanie | |
dc.contributor.author | Reccia, Isabella | |
dc.contributor.author | Lai, Hong-Shiee | |
dc.contributor.author | Peng, Ling | |
dc.contributor.author | Kostomitsopoulos, Nikos | |
dc.contributor.author | Nicholls, Joanna | |
dc.contributor.author | Habib, Robert | |
dc.contributor.author | Tomalia, Donald A. | |
dc.contributor.author | Sætrom, Pål | |
dc.contributor.author | Wilkes, Edmund | |
dc.contributor.author | Cutillas, Pedro | |
dc.contributor.author | Rossi, John | |
dc.contributor.author | Habib, Nagy | |
dc.date.accessioned | 2022-05-04T11:44:03Z | |
dc.date.available | 2022-05-04T11:44:03Z | |
dc.date.created | 2020-09-17T16:30:04Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Molecular Therapy - Nucleic Acids. 2020, 19 361-370. | en_US |
dc.identifier.issn | 2162-2531 | |
dc.identifier.uri | https://hdl.handle.net/11250/2994173 | |
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. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.title | Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile | en_US |
dc.title.alternative | Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 361-370 | en_US |
dc.source.volume | 19 | en_US |
dc.source.journal | Molecular Therapy - Nucleic Acids | en_US |
dc.identifier.doi | 10.1016/j.omtn.2019.10.044 | |
dc.identifier.cristin | 1830951 | |
dc.relation.project | Norges forskningsråd: 230338 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |