Dietary Squalene Induces Cytochromes Cyp2b10 and Cyp2c55 Independently of Sex, Dose, and Diet in Several Mouse Models

• Published in: Molecular nutrition & food research 2020-10, Vol.64 (20), p.e2000354-n/a
• Main Authors: Gabás‐Rivera, Clara, Jurado‐Ruiz, Enrique, Sánchez‐Ortiz, Araceli, Romanos, Eduardo, Martínez‐Beamonte, Roberto, Navarro, María A., Surra, Joaquín C., Arnal, Carmen, Rodríguez‐Yoldi, María J., Andrés‐Lacueva, Cristina, Osada, Jesús
• Format: Article
• Language: English
• Subjects: Animal models; Apolipoprotein E; apolipoprotein E‐deficient mice; Cyp2b10 and Cyp2c55; Cytochrome; Cytochromes; Diet; Dietary supplements; Gene expression; Hormones; Lipids; Liver; Olive oil; Rodents; Sex; Sex hormones; Squalene
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202000354

Scope: To investigate the effects of squalene, the main hydrocarbon present in extra virgin olive oil, on liver transcriptome in different animal models and to test the influence of sex on this action and its relationship with hepatic lipids. Methods and Results: To this purpose, male C57BL/6J Apoe‐deficient mice are fed a purified Western diet with or without squalene during 11 weeks and hepatic squalene content is assessed, so are hepatic lipids and lipid droplets. Hepatic transcriptomic changes are studied and confirmed by RT‐qPCR. Dietary characteristics and influence of squalene doses are tested in Apoe‐deficient on purified chow diets with or without squalene. These diets are also given to Apoa1 and wild‐type mice on C57BL/6J background and to C57BL/6J xOla129 Apoe‐deficient mice. Squalene supplementation increases its hepatic content without differences among sexes and hormonal status. The Cyp2b10 and Cyp2c55 gene expressions are significantly up‐regulated by the squalene intake in all models, with independence of sex, sexual hormones, dietary fat content, genetic background and dose, and in Apoe‐deficient mice consuming extra‐virgin olive oil. Conclusion: Hepatic squalene increases the expression of these cytochromes and their changes in virgin olive oil diets may be due to their squalene content. Squalene administration activates two P450 cytochromes. Squalene‐enriched Western diet induces hepatic steatosis with higher squalene content and lower amount of triglycerides and protection of oxidative stress. The Cyp2b10 and Cyp2c55 gene expressions are significantly up‐regulated by the squalene intake, with independence of sex, sexual hormones, dietary fat content, genetic background and dose, and in Apoe‐deficient mice consuming extra‐virgin olive oil.