SIRT1 regulates hepatic vldlr levels
Background Endoplasmic reticulum (ER) stress-mediated increases in the hepatic levels of the very low-density lipoprotein (VLDL) receptor (VLDLR) promote hepatic steatosis by increasing the delivery of triglyceride-rich lipoproteins to the liver. Here, we examined whether the NAD(+)-dependent deacet...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/221900 |
| Acceso en línea: | https://hdl.handle.net/2445/221900 |
| Access Level: | acceso abierto |
| Palabra clave: | Malalties del fetge Trastorns del metabolisme dels lípids Liver diseases Lipid metabolism disorders |
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SIRT1 regulates hepatic vldlr levelsPeyman, MonaBabin-Ebell, AnnaRodríguez-Rodríguez, RosalíaRigon, MatildeAguilar-Recarte, DavidVillarroya i Terrade, JoanPlanavila Porta, AnaVillarroya i Gombau, FrancescPalomer Tarridas, Francesc XavierBarroso Fernández, EmmaVázquez Carrera, ManuelMalalties del fetgeTrastorns del metabolisme dels lípidsLiver diseasesLipid metabolism disordersBackground Endoplasmic reticulum (ER) stress-mediated increases in the hepatic levels of the very low-density lipoprotein (VLDL) receptor (VLDLR) promote hepatic steatosis by increasing the delivery of triglyceride-rich lipoproteins to the liver. Here, we examined whether the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1) regulates hepatic lipid accumulation by modulating VLDLR levels and the subsequent uptake of triglyceride-rich lipoproteins. Methods Rats fed with fructose in drinking water, Sirt1−/− mice, mice treated with the ER stressor tunicamycin with or without a SIRT1 activator, and human Huh-7 hepatoma cells transfected with siRNA or exposed to tunicamycin or different inhibitors were used. Results Hepatic SIRT1 protein levels were reduced, while those of VLDLR were upregulated in the rat model of metabolic dysfunction-associated steatotic liver disease (MASLD) induced by fructose-drinking water. Moreover, Sirt1−/− mice displayed increased hepatic VLDLR levels that were not associated with ER stress, but were accompanied by an increased expression of hypoxia-inducible factor 1α (HIF-1α)-target genes. The pharmacological inhibition or gene knockdown of SIRT1 upregulated VLDLR protein levels in the human Huh-7 hepatoma cell line, with this increase abolished by the pharmacological inhibition of HIF-1α. Finally, SIRT1 activation prevented the increase in hepatic VLDLR protein levels in mice treated with the ER stressor tunicamycin. Conclusions Overall, these findings suggest that SIRT1 attenuates fatty liver development by modulating hepatic VLDLR levels.BioMed Central2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/221900Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12964-024-01666-yCell Communication and Signaling, 2024, vol. 22, p. 297https://doi.org/10.1186/s12964-024-01666-ycc-by (c) Peyman, M. et al., 2024http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2219002026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
SIRT1 regulates hepatic vldlr levels |
| title |
SIRT1 regulates hepatic vldlr levels |
| spellingShingle |
SIRT1 regulates hepatic vldlr levels Peyman, Mona Malalties del fetge Trastorns del metabolisme dels lípids Liver diseases Lipid metabolism disorders |
| title_short |
SIRT1 regulates hepatic vldlr levels |
| title_full |
SIRT1 regulates hepatic vldlr levels |
| title_fullStr |
SIRT1 regulates hepatic vldlr levels |
| title_full_unstemmed |
SIRT1 regulates hepatic vldlr levels |
| title_sort |
SIRT1 regulates hepatic vldlr levels |
| dc.creator.none.fl_str_mv |
Peyman, Mona Babin-Ebell, Anna Rodríguez-Rodríguez, Rosalía Rigon, Matilde Aguilar-Recarte, David Villarroya i Terrade, Joan Planavila Porta, Ana Villarroya i Gombau, Francesc Palomer Tarridas, Francesc Xavier Barroso Fernández, Emma Vázquez Carrera, Manuel |
| author |
Peyman, Mona |
| author_facet |
Peyman, Mona Babin-Ebell, Anna Rodríguez-Rodríguez, Rosalía Rigon, Matilde Aguilar-Recarte, David Villarroya i Terrade, Joan Planavila Porta, Ana Villarroya i Gombau, Francesc Palomer Tarridas, Francesc Xavier Barroso Fernández, Emma Vázquez Carrera, Manuel |
| author_role |
author |
| author2 |
Babin-Ebell, Anna Rodríguez-Rodríguez, Rosalía Rigon, Matilde Aguilar-Recarte, David Villarroya i Terrade, Joan Planavila Porta, Ana Villarroya i Gombau, Francesc Palomer Tarridas, Francesc Xavier Barroso Fernández, Emma Vázquez Carrera, Manuel |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Malalties del fetge Trastorns del metabolisme dels lípids Liver diseases Lipid metabolism disorders |
| topic |
Malalties del fetge Trastorns del metabolisme dels lípids Liver diseases Lipid metabolism disorders |
| description |
Background Endoplasmic reticulum (ER) stress-mediated increases in the hepatic levels of the very low-density lipoprotein (VLDL) receptor (VLDLR) promote hepatic steatosis by increasing the delivery of triglyceride-rich lipoproteins to the liver. Here, we examined whether the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1) regulates hepatic lipid accumulation by modulating VLDLR levels and the subsequent uptake of triglyceride-rich lipoproteins. Methods Rats fed with fructose in drinking water, Sirt1−/− mice, mice treated with the ER stressor tunicamycin with or without a SIRT1 activator, and human Huh-7 hepatoma cells transfected with siRNA or exposed to tunicamycin or different inhibitors were used. Results Hepatic SIRT1 protein levels were reduced, while those of VLDLR were upregulated in the rat model of metabolic dysfunction-associated steatotic liver disease (MASLD) induced by fructose-drinking water. Moreover, Sirt1−/− mice displayed increased hepatic VLDLR levels that were not associated with ER stress, but were accompanied by an increased expression of hypoxia-inducible factor 1α (HIF-1α)-target genes. The pharmacological inhibition or gene knockdown of SIRT1 upregulated VLDLR protein levels in the human Huh-7 hepatoma cell line, with this increase abolished by the pharmacological inhibition of HIF-1α. Finally, SIRT1 activation prevented the increase in hepatic VLDLR protein levels in mice treated with the ER stressor tunicamycin. Conclusions Overall, these findings suggest that SIRT1 attenuates fatty liver development by modulating hepatic VLDLR levels. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/221900 |
| url |
https://hdl.handle.net/2445/221900 |
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Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1186/s12964-024-01666-y Cell Communication and Signaling, 2024, vol. 22, p. 297 https://doi.org/10.1186/s12964-024-01666-y |
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cc-by (c) Peyman, M. et al., 2024 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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cc-by (c) Peyman, M. et al., 2024 http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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BioMed Central |
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BioMed Central |
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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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