Squalene through its post-squalene metabolites is a modulator of hepatic transcriptome in rabbits

Abuobeid, R. ; Sánchez-Marco, J. ; Felices, M. J. ; Arnal, C. (Universidad de Zaragoza) ; Burillo, J. C. ; Lasheras, R. ; Busto, R. ; Lasunción, M. A. ; Rodríguez-Yoldi, M. J. (Universidad de Zaragoza) ; Martínez-Beamonte, R. (Universidad de Zaragoza) ; Osada, J. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/ijms23084172

Año: 2022

Publicado en: International Journal of Molecular Sciences 23, 8 (2022), 4172 [16 pp]
ISSN: 1661-6596

Factor impacto JCR: 5.6 (2022)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 66 / 285 = 0.232 (2022) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 178 = 0.292 (2022) - Q2 - T1

Factor impacto CITESCORE: 7.8 - Biochemistry, Genetics and Molecular Biology (Q1) - Computer Science (Q1) - Chemistry (Q1) - Chemical Engineering (Q1) - Medicine (Q1)

Factor impacto SCIMAGO: 1.154 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/CIBERObn/CB06/03/0021
Financiación: info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/B16-20R
Financiación: info:eu-repo/grantAgreement/ES/MICINN-ISCIIII-FEDER/PID2019-104915RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098113-B100
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/Redvalue-SOE1-PI-E0123

Tipo y forma: Article (Published version)

Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)