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862369.pdf (1.88 MB)

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2024-12-01

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cc-by (c) Peyman, M. et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221900

SIRT1 regulates hepatic vldlr levels

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Recurs relacionat

https://doi.org/10.1186/s12964-024-01666-y

Resum

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.

Matèries

Malalties del fetge, Trastorns del metabolisme dels lípids

Matèries (anglès)

Liver diseases, Lipid metabolism disorders

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

Citació

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. SIRT1 regulates hepatic vldlr levels. _Cell Communication and Signaling_. 2024. Vol. 22, núm. 297. [consulta: 3 de gener de 2026]. ISSN: 1478-811X. [Disponible a: https://hdl.handle.net/2445/221900]

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