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

Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes
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 [d5]-18:3n-3 to longer chain fatty acids. Progesterone, but not 17?-ethynylestradiol or testosterone, increased FADS2, FADS1, ELOVl 5 and ELOVl 2 mRNA expression in HepG2 cells and in primary human hepatocytes. In HepG2 cells, these changes were accompanied by hypomethylation of specific CpG loci in the FADS2 promoter. Progesterone, but not 17?-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
47-54
Sibbons, Charlene
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Brenna, J. Thomas
48f80b56-bd2a-4341-a414-c96a03855849
Lawrence, Peter
d77c5133-428f-4465-bb28-2cd5e2b41b88
Hoile, Samuel
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Clarke-Harris, Rebecca
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Lillycrop, Karen
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Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Sibbons, Charlene
e613c761-bc82-4511-afd6-2d7e3cccc038
Brenna, J. Thomas
48f80b56-bd2a-4341-a414-c96a03855849
Lawrence, Peter
d77c5133-428f-4465-bb28-2cd5e2b41b88
Hoile, Samuel
9d7e9816-600d-45bd-ade2-dc7798bba730
Clarke-Harris, Rebecca
7fc6eb8b-28cb-48cf-926f-84a9fd05b363
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159

Sibbons, Charlene, Brenna, J. Thomas, Lawrence, Peter, Hoile, Samuel, Clarke-Harris, Rebecca, Lillycrop, Karen and Burdge, Graham (2014) Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes. Prostaglandins, Leukotrienes and Essential Fatty Acids, 90 (2-3), 47-54. (doi:10.1016/j.plefa.2013.12.006). (PMID:24411721)

Record type: Article

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 17?-ethynylestradiol or testosterone, increased FADS2, FADS1, ELOVl 5 and ELOVl 2 mRNA expression in HepG2 cells and in primary human hepatocytes. In HepG2 cells, these changes were accompanied by hypomethylation of specific CpG loci in the FADS2 promoter. Progesterone, but not 17?-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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PLEFA Hormones and PUFA Accepted.docx - Accepted Manuscript
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e-pub ahead of print date: 18 December 2013
Published date: January 2014
Organisations: Human Development & Health

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Local EPrints ID: 365682
URI: http://eprints.soton.ac.uk/id/eprint/365682
PURE UUID: 911c4437-0d74-40b1-950d-b8d039f56378
ORCID for Rebecca Clarke-Harris: ORCID iD orcid.org/0000-0002-6888-9518
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Graham Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 12 Jun 2014 13:16
Last modified: 15 Mar 2024 03:36

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Contributors

Author: Charlene Sibbons
Author: J. Thomas Brenna
Author: Peter Lawrence
Author: Samuel Hoile
Author: Rebecca Clarke-Harris ORCID iD
Author: Karen Lillycrop ORCID iD
Author: Graham Burdge ORCID iD

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