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http://hdl.handle.net/2445/171056
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DC Field | Value | Language |
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dc.contributor.author | Barroso Fernández, Emma | - |
dc.contributor.author | Rodríguez-Rodríguez, Rosalia | - |
dc.contributor.author | Zarei, Mohammad | - |
dc.contributor.author | Pizarro Delgado, Javier | - |
dc.contributor.author | Planavila Porta, Ana | - |
dc.contributor.author | Palomer Tarridas, Francesc Xavier | - |
dc.contributor.author | Villarroya i Gombau, Francesc | - |
dc.contributor.author | Vázquez Carrera, Manuel | - |
dc.date.accessioned | 2020-10-06T08:20:15Z | - |
dc.date.available | 2020-10-06T08:20:15Z | - |
dc.date.issued | 2020-09-10 | - |
dc.identifier.issn | 1478-811X | - |
dc.identifier.uri | http://hdl.handle.net/2445/171056 | - |
dc.description.abstract | Background: Deficiency of mitochondrial sirtuin 3 (SIRT3), a NAD+ -dependent protein deacetylase that maintains redox status and lipid homeostasis, contributes to hepatic steatosis. In this study, we investigated additional mechanisms that might play a role in aggravating hepatic steatosis in Sirt3-deficient mice fed a high-fat diet (HFD). Methods: Studies were conducted in wild-type (WT) and Sirt3−/− mice fed a standard diet or a HFD and in SIRT3- knockdown human Huh-7 hepatoma cells. Results: Sirt3−/− mice fed a HFD presented exacerbated hepatic steatosis that was accompanied by decreased expression and DNA-binding activity of peroxisome proliferator-activated receptor (PPAR) α and of several of its target genes involved in fatty acid oxidation, compared to WT mice fed the HFD. Interestingly, Sirt3 deficiency in liver and its knockdown in Huh-7 cells resulted in upregulation of the nuclear levels of LIPIN1, a PPARα co-activator, and of the protein that controls its levels and localization, hypoxia-inducible factor 1α (HIF-1α). These changes were prevented by lipid exposure through a mechanism that might involve a decrease in succinate levels. Finally, Sirt3−/− mice fed the HFD showed increased levels of some proteins involved in lipid uptake, such as CD36 and the VLDL receptor. The upregulation in CD36 was confirmed in Huh-7 cells treated with a SIRT3 inhibitor or transfected with SIRT3 siRNA and incubated with palmitate, an effect that was prevented by the Nrf2 inhibitor ML385. Conclusion: These findings demonstrate new mechanisms by which Sirt3 deficiency contributes to hepatic steatosis | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/s12964-020-00640-8 | - |
dc.relation.ispartof | Cell Communication and Signaling, 2020, vol. 18, num. 147 | - |
dc.relation.uri | https://doi.org/10.1186/s12964-020-00640-8 | - |
dc.rights | cc-by (c) Barroso Fernández, Emma et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Malalties del fetge | - |
dc.subject.classification | Lípids | - |
dc.subject.other | Liver diseases | - |
dc.subject.other | Lipids | - |
dc.title | SIRT3 deficiency exacerbates fatty liver by attenuating the HIF1α-LIPIN 1 pathway and increasing CD36 through Nrf2 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 703469 | - |
dc.date.updated | 2020-10-06T08:20:15Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32912335 | - |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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703469.pdf | 2.68 MB | Adobe PDF | View/Open |
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