Transcriptomics and epigenomics of rat born to dams fed a diet deficient in methyl group donors
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE60775 | GEO | 2015/06/22
SECONDARY ACCESSION(S): PRJNA259526
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-06-22 | E-GEOD-60775 | biostudies-arrayexpress
Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver methylome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. Modifications of DNA methylation were found in the promoter regions of 1,032 genes out of 14,981 genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function.
2015-06-22 | GSE59191 | GEO
Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver methylome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. Modifications of DNA methylation were found in the promoter regions of 1,032 genes out of 14,981 genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function. MDD induced modifications of methylation in rat liver were measured in 21-day-old rats born to dams fed with standard food or food deficient in methyl group donor. Six independent experiments were performed (3 controls versus 3 MDD).
2015-06-22 | E-GEOD-59191 | biostudies-arrayexpress
Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver transcriptome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. From a total of 44,000 probes for 26,456 genes, we found two gene clusters whose expression levels had statistically significant differences between control and deficient rats: 3,269 up-regulated and 2,841 down-regulated genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function.
2015-06-22 | GSE59039 | GEO
Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver transcriptome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. From a total of 44,000 probes for 26,456 genes, we found two gene clusters whose expression levels had statistically significant differences between control and deficient rats: 3,269 up-regulated and 2,841 down-regulated genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function. Modifications of gene expression in rat liver were measured in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates). Eight independent experiments were performed (4 Controls versus 4 Methyl Donor Deficiency - MDD).
2015-06-22 | E-GEOD-59039 | biostudies-arrayexpress
Project description:Methyl deficiencies have been implicated in metabolic programming during the periods of oocyte and embryo development. Semisynthetic methyl-deficient diets (MD) with no folic acid, 0.05% choline, and approximately one-half the recommended content of methionine were fed to female rats for 3 wk prior to mating and for the first 5 d of gestation. During the period of MD feeding, plasma homocysteine concentrations were approximately twice those of rats fed the complete (CON) diet. From d 5, both groups received a complete semipurified AIN diet until birth. On d 8, plasma homocysteine concentrations did not differ between the 2 groups. Thereafter, dams and offspring were fed a nonpurified diet for the remainder of the experiment. At 6 mo of age, the homeostatic model assessment (HOMA) index of the male MD offspring tended to be 32% higher (P = 0.053) and peak insulin during an oral glucose tolerance test (oGTT) was 39% higher (P < 0.05) compared with the male CON offspring. There was no difference in the response to an oGTT in the female offspring at 6 mo of age. The increased HOMA index of male MD offspring persisted to 12 mo of age. The peak glucose concentration during oGTT was 23% higher (P < 0.05) in MD compared with the CON males despite 39% greater (P < 0.05) peak insulin concentrations. This study shows that in rats, a physiologically relevant methyl-deficient diet fed during the period of oocyte maturation and preimplantation development programs gender-specific changes in glucose handling by the offspring.
| S-EPMC3001237 | biostudies-literature
Project description:BackgroundMetabolic and endocrine environment during early life is crucial for metabolic imprinting. When dams were fed a high fat diet (HF diet), rat offspring developed hypothalamic leptin resistance with lean phenotype when weaned on a normal diet. Interestingly, when grown on the HF diet, they appeared to be protected against the effects of HF diet as compared to offspring of normally fed dams. The mechanisms involved in the protective effect of maternal HF diet are unclear.Methodology/principal findingsWe thus investigated the impact of maternal high fat diet on offspring subjected to normal or high palatable diet (P diet) on metabolic and endocrine parameters. We compared offspring born to dams fed P or HF diet. Offspring born to dams fed control or P diet, when fed P diet exhibited a higher body weight, altered hypothalamic leptin sensitivity and metabolic parameters suggesting that maternal P diet has no protective effect on offspring. Whereas, maternal HF diet reduces body weight gain and circulating triglycerides, and ameliorates corpulence index of offspring, even when subjected to P diet. Interestingly, this protective effect is differently expressed in male and female offspring. Male offspring exhibited higher energy expenditure as mirrored by increased hypothalamic UCP-2 and liver AdipoR1/R2 expression, and a profound change in the arcuate nucleus astrocytic organization. In female offspring, the most striking impact of maternal HF diet is the reduced hypothalamic expression of NPY and POMC.Conclusions/significanceHF diet given during gestation and lactation protects, at least partially, offspring from excessive weight gain through several mechanisms depending upon gender including changes in arcuate nucleus astrocytic organization and increased hypothalamic UCP-2 and liver AdipoR1/2 expression in males and reduced hypothalamic expression of NPY and POMC in females. Taken together our results reveal new mechanisms involved in the protective effect of maternal HF diet.
| S-EPMC3064582 | biostudies-literature
Project description:A progressive decrease was observed in the 5-methyldeoxycytidine content of hepatic DNA in male F344 rats fed with a hepatocarcinogenic methyl-deficient diet. The same dietary regimen resulted in altered hepatic contents of S-adenosylmethionine, the methyl-donating species, and S-adenosylhomocysteine, an inhibitor of DNA methylase. The data indicate that this carcinogenic dietary manipulation is sufficient to alter a possible regulatory process, DNA methylation.
| S-EPMC1153433 | biostudies-other
Project description:Diet changes can partly explain the high burden of asthma in industrialised nations. Findings from experimental studies have stimulated many observational studies of the association between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. However, observational studies are susceptible to several sources of bias; well conducted randomised controlled trials (RCTs) are the gold standard to establish whether diet has an effect on asthma. Evidence from observational studies and a few RCTs strongly justifies ongoing and future RCTs in three areas: vitamin D for the prevention or treatment of asthma, choline supplementation as adjuvant treatment for asthma, and vitamin E to prevent the detrimental effects of air pollution in patients with asthma. At present, insufficient evidence exists to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma.
| S-EPMC3904132 | biostudies-literature
Project description:Background/aimsThe importance of epigenetic changes in etiology and pathogenesis of disease has been increasingly recognized. However, the role of epigenetic alterations in the genesis of hepatic steatosis and cause of individual susceptibilities to this pathological state are largely unknown.MethodsMale inbred C57BL/6J and DBA/2J mice were fed a lipogenic methyl-deficient diet (MDD) that causes liver injury similar to human non-alcoholic steatohepatitis (NASH) for 6, 12, or 18 weeks, and the status of global and repetitive elements cytosine methylation, histone modifications, and expression of proteins responsible for those epigenetic modifications in livers was determined.ResultsThe development of hepatic steatosis in inbred C57BL/6J and DBA/2J mice was accompanied by prominent epigenetic abnormalities. This was evidenced by pronounced loss of genomic and repetitive sequences cytosine methylation, especially at major and minor satellites, accompanied by increased levels of repeat-associated transcripts, aberrant histone modifications, and alterations in expression of the maintenance DNA methyltransferase 1 (DNMT1) and de novo DNMT3A proteins in the livers of both mouse strains. However, the DBA/2J mice, which were characterized by an initially lower degree of methylation of repetitive elements and lower extent of histone H3 lysine 9 (H3K9) and H3 lysine 27 (H3K27) trimethylation in the normal livers, as compared to those in the C57BL/6J mice, developed more prominent NASH-specific pathomorphological changes.ConclusionsThese results mechanistically link epigenetic alterations to the pathogenesis of hepatic steatosis and strongly suggest that differences in the cellular epigenetic status may be a predetermining factor to individual susceptibilities to hepatic steatosis.
| S-EPMC2773516 | biostudies-literature