117453 20240319081000.0 doi 10.3390/ijms23084172 sideral 128762 ART-2022-128762 eng Abuobeid, R. Squalene through its post-squalene metabolites is a modulator of hepatic transcriptome in rabbits 2022 Access copy available to the general public Unrestricted Squalene is a natural bioactive triterpene and an important intermediate in the biosynthesis of sterols. To assess the effect of this compound on the hepatic transcriptome, RNA-sequencing was carried out in two groups of male New Zealand rabbits fed either a diet enriched with 1% sunflower oil or the same diet with 0.5% squalene for 4 weeks. Hepatic lipids, lipid droplet area, squalene, and sterols were also monitored. The Squalene administration downregulated 9 transcripts and upregulated 13 transcripts. The gene ontology of transcripts fitted into the following main categories: transporter of proteins and sterols, lipid metabolism, lipogenesis, anti-inflammatory and anti-cancer properties. When the results were confirmed by RT-qPCR, rabbits receiving squalene displayed significant hepatic expression changes of LOC100344884 (PNPLA3), GCK, TFCP2L1, ASCL1, ACSS2, OST4, FAM91A1, MYH6, LRRC39, LOC108176846, GLT1D1 and TREH. A squalene-enriched diet increased hepatic levels of squalene, lanosterol, dihydrolanosterol, lathosterol, zymostenol and desmosterol. Strong correlations were found among specific sterols and some squalene-changed transcripts. Incubation of the murine AML12 hepatic cell line in the presence of lanosterol, dihydrolanosterol, zymostenol and desmosterol reproduced the observed changes in the expressions of Acss2, Fam91a1 and Pnpla3. In conclusion, these findings indicate that the squalene and post-squalene metabolites play important roles in hepatic transcriptional changes required to protect the liver against malfunction. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. info:eu-repo/grantAgreement/ES/CIBERObn/CB06/03/0021 info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012 info:eu-repo/grantAgreement/ES/DGA-FSE/B16-20R info:eu-repo/grantAgreement/ES/MICINN-ISCIIII-FEDER/PID2019-104915RB-I00 info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098113-B100 info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/Redvalue-SOE1-PI-E0123 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.6 2022 BIOCHEMISTRY & MOLECULAR BIOLOGY 66 / 285 = 0.232 2022 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 52 / 178 = 0.292 2022 Q2 T1 1.154 2022 Medicine (miscellaneous) 2022 Q1 Physical and Theoretical Chemistry 2022 Q1 Computer Science Applications 2022 Q1 Inorganic Chemistry 2022 Q1 Spectroscopy 2022 Q1 Organic Chemistry 2022 Q1 Molecular Biology 2022 Q2 Catalysis 2022 Q2 7.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sánchez-Marco, J. (orcid)0000-0002-9023-741X Felices, M. J. Arnal, C. Universidad de Zaragoza (orcid)0000-0003-1197-4276 Burillo, J. C. Lasheras, R. Busto, R. Lasunción, M. A. Rodríguez-Yoldi, M. J. Universidad de Zaragoza (orcid)0000-0002-3595-7668 Martínez-Beamonte, R. Universidad de Zaragoza (orcid)0000-0002-8100-5596 Osada, J. Universidad de Zaragoza (orcid)0000-0002-8251-8457 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 23, 8 (2022), 4172 [16 pp] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 3788116 http://zaguan.unizar.es/record/117453/files/texto_completo.pdf Versión publicada 2749774 http://zaguan.unizar.es/record/117453/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117453 articulos driver 2024-03-18-14:01:50 ARTICLE