Dietary Erythrodiol Modifies Hepatic Transcriptome in Mice in a Sex and Dose-Dependent Way

• Main Authors: Roubi Abuobeid, Luis Herrera-Marcos, María A. Navarro, Carmen Arnal, Roberto Martínez-Beamonte, Joaquín Surra, Jesús Osada
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: erythrodiol; mice; liver; apolipoprotein E; olive oil; transcriptome
• Online Access: https://www.mdpi.com/1422-0067/21/19/7331

Erythrodiol is a terpenic compound found in a large number of plants. To test the hypotheses that its long-term administration may influence hepatic transcriptome and this could be influenced by the presence of APOA1-containing high-density lipoproteins (HDL), Western diets containing 0.01% of erythrodiol (10 mg/kg dose) were provided to <i>Apoe</i>- and <i>Apoa1</i>-deficient mice. Hepatic RNA-sequencing was carried out in male <i>Apoe</i>-deficient mice fed purified Western diets differing in the erythrodiol content. The administration of this compound significantly up- regulated 68 and down-regulated 124 genes at the level of 2-fold change. These genes belonged to detoxification processes, protein metabolism and nucleic acid related metabolites. Gene expression changes of 21 selected transcripts were verified by RT-qPCR. <i>Ccl19-ps2</i>, <i>Cyp2b10</i>, <i>Rbm14-rbm4</i>, <i>Sec61g</i>, <i>Tmem81</i>, <i>Prtn3</i>, <i>Amy2a5</i>, <i>Cyp2b9</i> and <i>Mup1</i> showed significant changes by erythrodiol administration. When <i>Cyp2b10</i>, <i>Dmbt1</i>, <i>Cyp2b13</i>, <i>Prtn3 and Cyp2b9</i> were analyzed in female <i>Apoe</i>-deficient mice, no change was observed. Likewise, no significant variation was observed in <i>Apoa1</i>- or in <i>Apoe-</i>deficient mice receiving doses ranging from 0.5 to 5 mg/kg erythrodiol. Our results give evidence that erythrodiol exerts a hepatic transcriptional role, but this is selective in terms of sex and requires a threshold dose. Furthermore, it requires an APOA1-containing HDL.