Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes

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 [d(5)]-18:3n-3 to longer chain fatty acids. Progesterone, but not 17 alpha-ethynylestradiol or testosterone, increased FADS2, FADS1, ELOVI 5 and ELOV1 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 17a-ethynylestradiol or testosterone, increased conversion of [d(5)]-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. (C) 2013 Elsevier Ltd. All rights reserved.