Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes |
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| Institution: | 1. Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK;2. NIHR Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK;3. Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK;4. Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), Singapore;5. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK;6. Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK;7. Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia;8. Department of Paediatrics, KK Women''s and Children''s Hospital, Singapore;9. Duke NUS Graduate School of Medicine, Singapore;10. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore;11. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;12. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;13. Centre for Genetics of Health and Disease, University of Western, Australia;14. Faculty of Health Science, Curtin University, Australia;15. School of Medicine and Pharmacology, University of Western Australia, Australia;p. Telethon Kids Institute, University of Western Australia, Perth, Australia;q. Liggins Institute, University of Auckland, Auckland, New Zealand |
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| Abstract: | Female humans and rodents have been shown to have higher 22:6n-3 status and synthesis than males. It is unclear which sex hormone is involved. We investigated the specificity of the effects of physiological concentrations of sex hormones in vitro on the mRNA expression of genes involved in polyunsaturated fatty acid (PUFA) biosynthesis and on the conversion of d5]-18:3n-3 to longer chain fatty acids. Progesterone, but not 17α-ethynylestradiol or testosterone, increased FADS2, FADS1, ELOVl 5 and ELOVl 2 mRNA expression in HepG2 cells, but only FADS2 in primary human hepatocytes. In HepG2 cells, these changes were accompanied by hypomethylation of specific CpG loci in the FADS2 promoter. Progesterone, not 17α-ethynylestradiol or testosterone, increased conversion of d5]-18:3n-3 to 20:5n-3, 22:5n-3 and 22:6n-3. These findings show that progesterone increases n-3 PUFA biosynthesis by up-regulating the mRNA expression of genes involved in this pathway, possibly via changes in the epigenetic regulation of FADS2. |
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| Keywords: | Omega-3 polyunsaturated fatty acids Eicosapentaenoic acid Docosahexaenoic acid Estrogen Progesterone Testosterone FADS Elongase |
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