title: 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.
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.
  
  
  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.
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Hoile
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Clarke-Harris
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Rae-Chi
authors.initials: RC
authors.lastname: Huang
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Beilin
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Lillycrop
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Graham C
authors.initials: GC
authors.lastname: Burdge
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D019175:DNA Methylation; D000090943:Delta-5 Fatty Acid Desaturase; D019587:Dietary Supplements; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D000081031:Fatty Acid Elongases; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000069463:Olive Oil; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism*
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; C000630967:ELOVL2 protein, human; C000630954:ELOVL5 protein, human; D015525:Fatty Acids, Omega-3; D000069463:Olive Oil; D010938:Plant Oils; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases