title: Maternal fat intake in rats alters 20:4n-6 and 22:6n-3 status and the epigenetic regulation of Fads2 in offspring liver.
abstract: Poor prenatal nutrition, acting through epigenetic processes, induces persistent changes in offspring phenotype. We investigated the effect of maternal fat intake on polyunsaturated fatty acid (PUFA) status and on the epigenetic regulation of Fads2, encoding Δ6 desaturase (rate limiting in PUFA synthesis), in the adult offspring. Rats (n=6 per dietary group) were fed either 3.5% (w/w), 7% (w/w) or 21% (w/w) butter or fish oil (FO) from 14 days preconception until weaning. Offspring (n=6 males and females per dietary group) were fed 4% (w/w) soybean oil until postnatal day 77. 20:4n-6 and 22:6n-3 levels were lower in liver phosphatidylcholine (PC) and phosphatidylethanolamine and plasma PC (all P<.0001) in offspring of dams fed 21% than 3.5% or 7% fat regardless of type. Hepatic Fads2 expression related inversely to maternal dietary fat. Fads2 messenger RNA expression correlated negatively with methylation of CpGs at -623, -394, -84 and -76 bases relative to the transcription start site (all P<.005). Methylation of these CpGs was higher in offspring of dams fed 21% than 3.5% or 7% fat; FO higher than butter. Feeding adult female rats 7% fat reduced 20:4n-6 status in liver PC and Fads2 expression and increased methylation of CpGs -623, -394, -84 and -76 that reversed in animals switched from 7% to 4% fat diets. These findings suggest that fat exposure during development induces persistent changes, while adults exhibit a transient response, in hepatic PUFA status in offspring through epigenetic regulation of Fads2. Thus, epigenetic regulation of Fads2 may contribute to short- and long-term regulation of PUFA synthesis.
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Hoile
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Irvine
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kelsall
authors.forename: Charlene
authors.initials: C
authors.lastname: Sibbons
authors.forename: Aurélie
authors.initials: A
authors.lastname: Feunteun
authors.forename: Alex
authors.initials: A
authors.lastname: Collister
authors.forename: Christopher
authors.initials: C
authors.lastname: Torrens
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Karen A
authors.initials: KA
authors.lastname: Lillycrop
authors.forename: Graham C
authors.initials: GC
authors.lastname: Burdge
mesh_terms: D000818:Animals; D018899:CpG Islands; D004041:Dietary Fats / Q000008:administration & dosage*; D044127:Epigenesis, Genetic; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D012333:RNA, Messenger; D013230:Stearoyl-CoA Desaturase; C474452:delta 6-desaturase, rat