British Journal of Nutrition

Short Communication

Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPARα promoter of the offspring

Karen A. Lillycropa1, Emma S. Phillipsa1, Christopher Torrensa2, Mark A. Hansona2, Alan A. Jacksona3 and Graham C. Burdgea4 c1

a1 Development and Cell Biology, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK

a2 Institute of Developmental Sciences Building, Centre for DOHaD, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

a3 Institute of Human Nutrition, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

a4 Institute of Human Nutrition, Institute of Developmental Sciences Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

Abstract

Induction of an altered phenotype by prenatal under-nutrition involves changes in the epigenetic regulation of specific genes. We investigated the effect of feeding pregnant rats a protein-restricted (PR) diet with different amounts of folic acid on the methylation of individual CpG dinucleotides in the hepatic PPARα promoter in juvenile offspring, and the effect of the maternal PR diet on CpG methylation in adult offspring. Pregnant rats (five per group) were fed 180 g/kg casein (control) or 90 g/kg casein with 1 mg/kg folic acid (PR), or 90 g/kg casein and 5 mg/kg folic acid (PRF). Offspring were killed on postnatal day 34 (five males and females per group) and day 80 (five males per group). Methylation of sixteen CpG dinucleotides in the PPARα promoter was measured by pyrosequencing. Mean PPARα promoter methylation in the PR offspring (4·5 %) was 26 % lower than controls (6·1 %) due to specific reduction at CpG dinucleotides 2 (40 %), 3 (43 %), 4 (33 %) and 16 (48 %) (P < 0·05). There was no significant difference in methylation at these CpG between control and PRF offspring. Methylation of CpG 5 and 8 was higher (47 and 63 %, respectively, P < 0·05) in the PRF offspring than control or PR offspring. The methylation pattern in day 80 PR offspring was comparable to day 34 PR offspring. These data show for the first time that prenatal nutrition induces differential changes to the methylation of individual CpG dinucleotides in juvenile rats which persist in adults.

(Received March 28 2007)

(Revised November 19 2007)

(Accepted November 20 2007)

(Online publication February 18 2008)

Correspondence:

c1 Corresponding author: Dr G. C. Burdge, fax +44 23 8079 5255, email g.c.burdge@soton.ac.uk

Footnotes

Abbreviations: GR, glucocorticoid receptor; PR diet, protein-restricted diet (90 g/kg casein and 1 mg/kg folic acid); PRF diet, protein-restricted diet with increased folic acid (90 g/kg casein and 5 mg/kg folic acid)

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