Nutrient-Gene Interactions Dietary Protein Restriction of Pregnant Rats Induces and Folic Acid Supplementation Prevents Epigenetic Modification of Hepatic Gene Expression in the Offspring
نویسندگان
چکیده
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. J. Nutr. 135: 1382–1386, 2005.
منابع مشابه
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 unbal...
متن کاملMaternal protein restriction with or without folic acid supplementation during pregnancy alters the hepatic transcriptome in adult male rats.
Feeding pregnant rats a protein-restricted (PR) diet induces altered expression of candidate genes in the liver of the adult offspring, which can be prevented by supplementation of the PR diet with folic acid (PRF). We investigated the effect of maternal nutrition during pregnancy on the liver transcriptome in their adult male offspring. Pregnant rats were fed control, PR or PRF diets. Male off...
متن کاملFolic acid supplementation in pregnancy: Are there devils in the detail?
Maternal folic acid (FA) supplementation is well recognised to protect against neural tube defects. Folate is a critical cofactor in one-carbon metabolism involved in the epigenetic regulation of transcription that underpins development. Thus, it is possible that maternal FA supplementation may have additional, unforeseen persistent effects in the offspring. This is supported by the modificatio...
متن کاملEffects of feed restriction and dietary fat type on mRNA expression of liver fatty acid-binding protein (L-FABP) in broilers
Background: Liver fatty acid-binding protein (L-FABP) is the main cytosolic binding site for long chain fatty acids in hepatocytes. FABPs enhance the uptake of fatty acids into the cell by increasing their concentration due to decreasing concentration of unbound fatty acids inside the cell. Objectives: The aim of this study was to evaluate the effects of dietary unsaturated to saturated fatty a...
متن کاملEffect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early Weanling Intrauterine Growth Retarded Rats.
BACKGROUND/AIMS The objective of this study was to examine the responses of p53 promoter methylation involved in kidney structure and function of early weaning intrauterine growth retarded (IUGR) rats to dietary folic acid supplementation. METHOD Sprague-Dawley rats were fed isocaloric diets containing either 21% protein diet (normal feed) or 10% protein diet throughout pregnancy and normal f...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2005