Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits
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 th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4172 |
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| author | Roubi Abuobeid Javier Sánchez-Marco María J. Felices Carmen Arnal Juan Carlos Burillo Roberto Lasheras Rebeca Busto Miguel A. Lasunción María Jesús Rodríguez-Yoldi Roberto Martínez-Beamonte Jesús Osada |
| author_facet | Roubi Abuobeid Javier Sánchez-Marco María J. Felices Carmen Arnal Juan Carlos Burillo Roberto Lasheras Rebeca Busto Miguel A. Lasunción María Jesús Rodríguez-Yoldi Roberto Martínez-Beamonte Jesús Osada |
| author_sort | Roubi Abuobeid |
| collection | DOAJ |
| description | 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 <i>LOC100344884</i> (<i>PNPLA3</i>), <i>GCK</i>, <i>TFCP2L1</i>, <i>ASCL1</i>, <i>ACSS2</i>, <i>OST4</i>, <i>FAM91A1</i>, <i>MYH6</i>, <i>LRRC39</i>, <i>LOC108176846</i>, <i>GLT1D1</i> and <i>TREH</i>. 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 <i>Acss2</i>, <i>Fam91a1</i> and <i>Pnpla3</i>. 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. |
| first_indexed | 2024-03-09T13:34:26Z |
| format | Article |
| id | doaj.art-b57a076721f546b7a94f7c9b0d232659 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:34:26Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b57a076721f546b7a94f7c9b0d2326592023-11-30T21:14:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238417210.3390/ijms23084172Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in RabbitsRoubi Abuobeid0Javier Sánchez-Marco1María J. Felices2Carmen Arnal3Juan Carlos Burillo4Roberto Lasheras5Rebeca Busto6Miguel A. Lasunción7María Jesús Rodríguez-Yoldi8Roberto Martínez-Beamonte9Jesús Osada10Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Patología Animal, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainLaboratorio Agroambiental, Servicio de Seguridad Agroalimentaria de la Dirección General de Alimentación y Fomento Agroalimentario, Gobierno de Aragón, E-50071 Zaragoza, SpainLaboratorio Agroambiental, Servicio de Seguridad Agroalimentaria de la Dirección General de Alimentación y Fomento Agroalimentario, Gobierno de Aragón, E-50071 Zaragoza, SpainCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, E-28029 Madrid, SpainCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, E-28029 Madrid, SpainDepartamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, SpainSqualene 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 <i>LOC100344884</i> (<i>PNPLA3</i>), <i>GCK</i>, <i>TFCP2L1</i>, <i>ASCL1</i>, <i>ACSS2</i>, <i>OST4</i>, <i>FAM91A1</i>, <i>MYH6</i>, <i>LRRC39</i>, <i>LOC108176846</i>, <i>GLT1D1</i> and <i>TREH</i>. 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 <i>Acss2</i>, <i>Fam91a1</i> and <i>Pnpla3</i>. 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.https://www.mdpi.com/1422-0067/23/8/4172squalenevirgin olive oilrabbitsmurineAML12 cell linelipid droplets |
| spellingShingle | Roubi Abuobeid Javier Sánchez-Marco María J. Felices Carmen Arnal Juan Carlos Burillo Roberto Lasheras Rebeca Busto Miguel A. Lasunción María Jesús Rodríguez-Yoldi Roberto Martínez-Beamonte Jesús Osada Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits International Journal of Molecular Sciences squalene virgin olive oil rabbits murine AML12 cell line lipid droplets |
| title | Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits |
| title_full | Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits |
| title_fullStr | Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits |
| title_full_unstemmed | Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits |
| title_short | Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits |
| title_sort | squalene through its post squalene metabolites is a modulator of hepatic transcriptome in rabbits |
| topic | squalene virgin olive oil rabbits murine AML12 cell line lipid droplets |
| url | https://www.mdpi.com/1422-0067/23/8/4172 |
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