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Supplementation with n-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells

Supplementation with n-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells
Supplementation with n-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells
BACKGROUND: Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans.

METHODS AND RESULTS: We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts.

CONCLUSIONS: These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function.
1932-6203
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Clarke-Harris, R.
7fc6eb8b-28cb-48cf-926f-84a9fd05b363
Huang, R.C.
77f83e65-a6d3-4ea2-a032-0ea924fc4920
Calder, P.C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Mori, T.A.
9e47710e-412b-4633-9481-5a335890de41
Beilin, L.J.
7728e5b8-3049-4273-bb16-d4f95088d91a
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Clarke-Harris, R.
7fc6eb8b-28cb-48cf-926f-84a9fd05b363
Huang, R.C.
77f83e65-a6d3-4ea2-a032-0ea924fc4920
Calder, P.C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Mori, T.A.
9e47710e-412b-4633-9481-5a335890de41
Beilin, L.J.
7728e5b8-3049-4273-bb16-d4f95088d91a
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159

Hoile, Samuel P., Clarke-Harris, R., Huang, R.C., Calder, P.C., Mori, T.A., Beilin, L.J., Lillycrop, Karen A. and Burdge, Graham C. (2014) Supplementation with n-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells. PLoS ONE, 9 (10), [e109896]. (doi:10.1371/journal.pone.0109896). (PMID:25329159)

Record type: Article

Abstract

BACKGROUND: Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans.

METHODS AND RESULTS: We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts.

CONCLUSIONS: These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function.

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e-pub ahead of print date: 17 October 2014
Published date: 17 October 2014
Organisations: Human Development & Health

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Local EPrints ID: 370694
URI: http://eprints.soton.ac.uk/id/eprint/370694
ISSN: 1932-6203
PURE UUID: 14f7c3db-92a4-4e66-9d39-c6822a37c950
ORCID for R. Clarke-Harris: ORCID iD orcid.org/0000-0002-6888-9518
ORCID for P.C. Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 04 Nov 2014 11:13
Last modified: 15 Mar 2024 03:36

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Contributors

Author: Samuel P. Hoile
Author: R. Clarke-Harris ORCID iD
Author: R.C. Huang
Author: P.C. Calder ORCID iD
Author: T.A. Mori
Author: L.J. Beilin

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