https://scholars.lib.ntu.edu.tw/handle/123456789/629344
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Andrikakou, Pinelopi | en_US |
dc.contributor.author | Reebye, Vikash | en_US |
dc.contributor.author | Vasconcelos, Daniel | en_US |
dc.contributor.author | Yoon, Sorah | en_US |
dc.contributor.author | Voutila, Jon | en_US |
dc.contributor.author | George, Andrew J T | en_US |
dc.contributor.author | Swiderski, Piotr | en_US |
dc.contributor.author | Habib, Robert | en_US |
dc.contributor.author | Catley, Matthew | en_US |
dc.contributor.author | Blakey, David | en_US |
dc.contributor.author | Habib, Nagy A | en_US |
dc.contributor.author | Rossi, John J | en_US |
dc.contributor.author | KAI-WEN HUANG | en_US |
dc.date.accessioned | 2023-03-17T03:27:54Z | - |
dc.date.available | 2023-03-17T03:27:54Z | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 2159-3337 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/629344 | - |
dc.description.abstract | Metabolic syndrome (MetS) is a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Sirtuin 1 (SIRT1), a highly conserved histone deacetylase, is characterized as a key metabolic regulator and protector against aging-associated pathologies, including MetS. In this study, we investigate the therapeutic potential of activating SIRT1 using small activating RNAs (saRNA), thereby reducing inflammatory-like responses and re-establishing normal lipid metabolism. SIRT1 saRNA significantly increased SIRT1 messenger RNA (mRNA) and protein levels in both lipopolysaccharide-stimulated and nonstimulated macrophages. SIRT1 saRNA significantly decreased inflammatory-like responses, by reducing mRNA levels of key inflammatory cytokines, such as Tumor Necrosis Factor alpha, Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), and chemokines Monocyte Chemoattractant Protein-1 and keratinocyte chemoattractant. SIRT1 overexpression also significantly reduced phosphorylation of nuclear factor-κB and c-Jun N-terminal kinase, both key signaling molecules for the inflammatory pathway. To investigate the therapeutic effect of SIRT1 upregulation, we treated a high-fat diet model with SIRT1 saRNA conjugated to a transferrin receptor aptamer for delivery to the liver and cellular internalization. Animals in the SIRT1 saRNA treatment arm demonstrated significantly decreased weight gain with a significant reduction in white adipose tissue, triglycerides, fasting glucose levels, and intracellular lipid accumulation. These suggest treatment-induced changes to lipid and glucose metabolism in the animals. The results of this study demonstrate that targeted activation of SIRT1 by saRNAs is a potential strategy to reverse MetS. | en_US |
dc.language.iso | en | en_US |
dc.publisher | MARY ANN LIEBERT, INC | en_US |
dc.relation.ispartof | Nucleic acid therapeutics | en_US |
dc.subject | LPS; SIRT1; metabolic syndrome; small activating RNA; transferrin receptor aptamer | en_US |
dc.title | Enhancing SIRT1 Gene Expression Using Small Activating RNAs: A Novel Approach for Reversing Metabolic Syndrome | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1089/nat.2021.0115 | - |
dc.identifier.pmid | 35895511 | - |
dc.identifier.scopus | 2-s2.0-85138513066 | - |
dc.identifier.isi | WOS:000838921100001 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85138513066 | - |
dc.relation.pages | 486 | en_US |
dc.relation.journalvolume | 32 | en_US |
dc.relation.journalissue | 6 | en_US |
dc.relation.pageend | 496 | en_US |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.orcid | 0000-0001-6375-8714 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學系 |
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