Folic Acid Supplementation during the Juvenile-Pubertal Period in Rats Modifies the Phenotype and Epigenotype Induced by Prenatal Nutrition
Institute of Human Nutrition. Journal of Nutrition
(Impact Factor: 3.88).
05/2009; 139(6):1054-60. DOI: 10.3945/jn.109.104653
Prenatal nutritional constraint is associated with increased risk of metabolic dysregulation in adulthood contingent on adult diet. In rats, folic acid supplementation of a protein-restricted (PR) diet during pregnancy prevents altered phenotype and epigenotype in the offspring induced by the PR diet. We hypothesized that increasing folic acid intake during the juvenile-pubertal (JP) period would reverse the effects of a maternal PR diet on the offspring. Rats were fed a control (C) or PR diet during pregnancy and AIN93G during lactation. Offspring were weaned on d 28 onto diets containing 1 mg [adequate folate (AF)] or 5 mg [folic acid-supplemented (FS)] folic acid/kg feed. After 28 d, all offspring were fed a high-fat (18% wt:wt) diet and killed on d 84. As expected, offspring of PR dams fed the AF diet had increased fasting plasma triglyceride (TAG) and beta-hydroxybutyrate (betaHB) concentrations. The FS diet induced increased weight gain, a lower plasma betaHB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPARalpha and glucocorticoid receptor promoter methylation increased in liver and insulin receptor promoter methylation decreased in liver and adipose tissue in FS compared with AF offspring, with reciprocal changes in mRNA expression irrespective of maternal diet. These findings show that increased folic acid intake during the JP period did not simply reverse the phenotype induced by the maternal diet. This may represent a period of plasticity when specific nutrient intakes may alter the phenotype of the offspring through epigenetic changes in specific genes.
Available from: Ala A Al Rajabi
- "However, Burdge et al. report increased weight gain and hepatic lipid accumulation in rats fed high-fat diet containing 5 mg/kg folic acid, compared with 1 mg/kg folic acid . Under high fat feeding, excessive folic acid supplementation may promote hepatic lipid accumulation by impairing fatty acid oxidation in the liver through decreased expression of cpt1a . These contradictory findings may be a consequence of differences in the fat content of the diet. "
[Show abstract] [Hide abstract]
ABSTRACT: Folate is an essential B vitamin required for the maintenance of AdoMet-dependent methylation. The liver is responsible for many methylation reactions that are used for post-translational modification of proteins, methylation of DNA, and the synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions where methylation capacity is compromised, including folate deficiency, are associated with impaired phosphatidylcholine synthesis resulting in non-alcoholic fatty liver disease and steatohepatitis. In addition, folate intake and folate status have been associated with changes in the expression of genes involved in lipid metabolism, obesity, and metabolic syndrome. In this review, we provide insight on the relationship between folate and lipid metabolism, and an outlook for the future of lipid-related folate research. © 2013 BioFactors, 2013.
BioFactors 05/2014; 40(3). DOI:10.1002/biof.1154 · 4.59 Impact Factor
Available from: Gioia Altobelli
- "The observation that folic acid supplementation prevented or reversed both the changes in gene expression, (in keeping with observations at later time points of development ) and the changes in DNA methylation is of considerable interest. A general disturbance of 1-carbon metabolism associated with maternal protein restriction (suggested by the dysregulation, rescued by folate, of Gnmt in MLP), is one candidate mechanism that may explain this. "
[Show abstract] [Hide abstract]
ABSTRACT: A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.
PLoS ONE 12/2013; 8(12):e82989. DOI:10.1371/journal.pone.0082989 · 3.23 Impact Factor
Available from: Zhaojia ge
- "We investigated the methylation patterns in DMRs of paternally imprinted gene H19, maternally imprinted genes Peg3 (paternally expressed 3), Snrpn (small nuclear ribo nucleo protein N), Igf2r (insulinlike growth factor 2 receptor), and Peg1 in oocytes of control and obese animals and their offspring. Because other studies have shown that the expression of leptin (Lep) and Ppar-α (peroxisome proliferatoractivated receptor α) is regulated by DNA methylation in their promoters and that the two genes are correlated to metabolism (Burdge et al. 2009; Cordero et al. 2011a, 2011b), we also investigated DNA methylation of these two genes. We also investigated DNA methyla tion patterns of intracisternal A particle (IAP) in oocytes. "
[Show abstract] [Hide abstract]
ABSTRACT: Maternal obesity has adverse effects on oocyte quality, embryo development and it also affects the health of the offspring.
To understand the underlying mechanisms responsible for these negative effects, we investigated the DNA methylation status of several imprinted genes and metabolism-related genes.
A high-fat-diet (HFD)-induced mouse model was utilized to analyze the DNA methylation of several imprinted genes and of metabolism-related genes in oocytes from obese mice and in oocytes and liver from their offspring by employing combined bisulfite restriction analysis (COBRA) and bisulfite sequencing (BS).
The DNA methylation of imprinted genes in oocytes was not altered in both obese mothers and their offspring, while DNA methylation of metabolism-related genes was changed. The DNA methylation level in the promoter of Leptin was significantly increased and that in the promoter of Ppar-alpha (Ppar-α) was reduced in oocytes of obese mice. The increased methylation of Leptin and decreased methylation of Ppar-α was also observed in the liver of female offspring from obese mothers (OHFD). The mRNA expressions of Leptin and Ppar-α were significantly altered in the liver of offspring from obese mothers. In OHFD oocytes, the DNA methylation level in the promoter of Ppar-α was increased.
These results indicate that DNA methylation patterns of several metabolism-related genes are not only changed in oocytes of obese mice, but also in oocytes and liver of their offspring. These data may contribute to elucidating the adverse effects of maternal obesity on reproduction and the offspring's health.
Environmental Health Perspectives 12/2013; 122(2). DOI:10.1289/ehp.1307047 · 7.98 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.