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Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring

Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring
Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring
Environmental constraints during early life result in phenotypic changes that can be associated with increased disease risk in later life. This suggests persistent alteration of gene transcription. DNA methylation, which is largely established in utero, provides a causal mechanism by which unbalanced prenatal nutrition results in such altered gene expression.
We investigated the effect of unbalanced maternal nutrition on the methylation status and expression of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring after weaning. Dams were fed a control protein (C; 180 g/kg protein plus 1 mg/kg folic acid), restricted protein (R; 90 g/kg casein plus 1 mg/kg folic acid), or restricted protein plus 5 mg/kg folic acid (RF) diet throughout pregnancy. Pups were killed 6 d after weaning (n = 10 per group).
Gene methylation was determined by methylation-sensitive PCR and mRNA expression by semiquantitative RT-PCR. PPAR gene methylation was 20.6% lower (P < 0.001) and expression 10.5-fold higher in R compared with C pups. GR gene methylation was 22.8% lower (P < 0.05) and expression 200% higher (P < 0.01) in R pups than in C pups.
The RF diet prevented these changes. PPAR methylation status and expression did not differ among the groups. Acyl-CoA oxidase expression followed that of PPAR. These results show that unbalanced prenatal nutrition induces persistent, gene-specific epigenetic changes that alter mRNA expression. Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming.
fetal programming, epigenetic regulation, transcription factor
0022-3166
1382-1386
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Phillips, Emma S.
36b8c608-f279-4239-87c0-32df46ced0c7
Jackson, Alan A.
c9a12d7c-b4d6-4c92-820e-890a688379ef
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Phillips, Emma S.
36b8c608-f279-4239-87c0-32df46ced0c7
Jackson, Alan A.
c9a12d7c-b4d6-4c92-820e-890a688379ef
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159

Lillycrop, Karen A., Phillips, Emma S., Jackson, Alan A., Hanson, Mark A. and Burdge, Graham C. (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. Journal of Nutrition, 135 (6), 1382-1386.

Record type: Article

Abstract

Environmental constraints during early life result in phenotypic changes that can be associated with increased disease risk in later life. This suggests persistent alteration of gene transcription. DNA methylation, which is largely established in utero, provides a causal mechanism by which unbalanced prenatal nutrition results in such altered gene expression.
We investigated the effect of unbalanced maternal nutrition on the methylation status and expression of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring after weaning. Dams were fed a control protein (C; 180 g/kg protein plus 1 mg/kg folic acid), restricted protein (R; 90 g/kg casein plus 1 mg/kg folic acid), or restricted protein plus 5 mg/kg folic acid (RF) diet throughout pregnancy. Pups were killed 6 d after weaning (n = 10 per group).
Gene methylation was determined by methylation-sensitive PCR and mRNA expression by semiquantitative RT-PCR. PPAR gene methylation was 20.6% lower (P < 0.001) and expression 10.5-fold higher in R compared with C pups. GR gene methylation was 22.8% lower (P < 0.05) and expression 200% higher (P < 0.01) in R pups than in C pups.
The RF diet prevented these changes. PPAR methylation status and expression did not differ among the groups. Acyl-CoA oxidase expression followed that of PPAR. These results show that unbalanced prenatal nutrition induces persistent, gene-specific epigenetic changes that alter mRNA expression. Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming.

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Published date: June 2005
Keywords: fetal programming, epigenetic regulation, transcription factor

Identifiers

Local EPrints ID: 25761
URI: https://eprints.soton.ac.uk/id/eprint/25761
ISSN: 0022-3166
PURE UUID: f0b5e199-deb5-42cd-8a87-539237a497f9
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 12 Apr 2006
Last modified: 27 Jul 2018 00:34

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Contributors

Author: Emma S. Phillips
Author: Alan A. Jackson
Author: Mark A. Hanson ORCID iD

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