Adverse maternal environments perturb hepatic DNA methylome and transcriptome prior to the adult-onset non-alcoholic fatty liver disease in mouse offspring
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE232812 | GEO | 2023/05/23
REPOSITORIES: GEO
Similar Datasets
Project description:Exposure to adverse early-life environment (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. The objective was to investigate whether and to what extent hepatic DNA methylome was perturbed prior to the development of NAFLD in offspring exposed to AME in mice. AME constituted maternal western diet and late-gestational stress. Male offspring livers at birth (d0) and weaning (d21) were used for evaluating DNA methylome and transcriptome using reduced representation of bisulfite sequencing and RNA-seq, respectively. We found AME caused 5,879 differentially methylated regions (DMRs) and zero differentially expressed gene (DEG) at d0, and 2,970 and 123, respectively at d21. Majority of the DMRs were distal from gene transcription start sites and did not correlate with DEGs. The DEGs at d21 were significantly en-riched in GO biological processes characteristic of liver metabolic functions. In conclusion, AME drove changes in hepatic DNA methylome which preceded perturbations in the hepatic metabolic transcriptome, which preceded the onset of NAFLD. We speculate that subtle impacts in dynamic enhancers lead to long-range regulatory changes that manifest over time as gene network alter-nations to increase the incidence of NAFLD later in life.
2023-05-23 | GSE232810 | GEO
Project description:Exposure to adverse early-life environment (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. The objective was to investigate whether and to what extent hepatic DNA methylome was perturbed prior to the development of NAFLD in offspring exposed to AME in mice. AME constituted maternal western diet and late-gestational stress. Male offspring livers at birth (d0) and weaning (d21) were used for evaluating DNA methylome and transcriptome using reduced representation of bisulfite sequencing and RNA-seq, respectively. We found AME caused 5,879 differentially methylated regions (DMRs) and zero differentially expressed gene (DEG) at d0, and 2,970 and 123, respectively at d21. Majority of the DMRs were distal from gene transcription start sites and did not correlate with DEGs. The DEGs at d21 were significantly en-riched in GO biological processes characteristic of liver metabolic functions. In conclusion, AME drove changes in hepatic DNA methylome which preceded perturbations in the hepatic metabolic transcriptome, which preceded the onset of NAFLD. We speculate that subtle impacts in dynamic enhancers lead to long-range regulatory changes that manifest over time as gene network alter-nations to increase the incidence of NAFLD later in life.
2023-05-23 | GSE232811 | GEO
Project description:Adverse maternal environments perturb hepatic DNA methylome and transcriptome prior to the adult-onset non-alcoholic fatty liver disease in mouse offspring
| PRJNA974001 | ENA
Project description:Adverse maternal environments perturb hepatic DNA methylome and transcriptome prior to the adult-onset non-alcoholic fatty liver disease in mouse offspring [RRBS]
| PRJNA974008 | ENA
Project description:Adverse maternal environments perturb hepatic DNA methylome and transcriptome prior to the adult-onset non-alcoholic fatty liver disease in mouse offspring [RNA-seq]
| PRJNA974009 | ENA
Project description:Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.
| S-EPMC9228996 | biostudies-literature
Project description:Background & aimsThe prevalence of non-alcoholic fatty liver disease (NAFLD) is rising in young adults, with potential implications for reproductive-aged women. Whether NAFLD during pregnancy confers more serious risks for maternal or perinatal health is unclear.MethodsUsing weighted discharge data from the US national inpatient sample, we evaluated temporal trends of NAFLD in pregnancies after 20 weeks gestation, and compared outcomes to pregnancies with other chronic liver diseases (CLDs) or no CLD. Study outcomes included preterm birth, postpartum hemorrhage, hypertensive complications (pre-eclampsia, eclampsia, and/or hemolysis, elevated liver enzymes, and low platelets syndrome), and maternal or fetal death. NAFLD prevalence was estimated by calendar year and temporal trends tested by linear regression. Outcomes were analyzed by logistic regression adjusted for age, race, multiple gestation, and pre-pregnancy diabetes, obesity, dyslipidemia and hypertension.ResultsAmong 18,574,225 pregnancies, 5,640 had NAFLD and 115,210 had other, non-NAFLD CLD. Pregnancies with NAFLD nearly tripled from 10.5/100,000 pregnancies in 2007 to 28.9/100,000 in 2015 (p <0.001). Compared to the other groups, patients with NAFLD during pregnancy more frequently experienced gestational diabetes (7-8% vs. 23%), hypertensive complications (4% vs. 16%), postpartum hemorrhage (3-5% vs. 6%), and preterm birth (5-7% vs. 9%), all p values ≤0.01. On adjusted analysis, compared to no CLD, NAFLD was associated with hypertensive complications, preterm birth, postpartum hemorrhage and possibly maternal (but not fetal) death.ConclusionThe prevalence of NAFLD in pregnancy has nearly tripled in the last decade and is independently associated with hypertensive complications, postpartum hemorrhage and preterm birth. NAFLD should be considered a high-risk obstetric condition, with clinical implications for pre-conception counseling and pregnancy care.Lay summaryThe prevalence of non-alcoholic fatty liver disease (NAFLD) in pregnancy has almost tripled over the past 10 years. Having NAFLD during pregnancy increases risks for both the mother and the baby, including hypertensive complications of pregnancy, bleeding after delivery, and preterm birth. Thus, pre-conception counseling is warranted with consideration of high-risk obstetric management among women with NAFLD in pregnancy.
| S-EPMC7438303 | biostudies-literature
Project description:BACKGROUND & AIMS:Little is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography. METHODS:We performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ?30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included. RESULTS:Approximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78). CONCLUSIONS:Individuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.
| S-EPMC6758911 | biostudies-literature
Project description:Early life nutritional imbalances are risk factors for metabolic dysfunctions in adulthood, but the long term effects of perinatal exposure to high versus low protein diets are not completely understood. We exposed C57BL/6J offspring to a high protein/low carbohydrate (HP/LC) or low protein/high carbohydrate (LP/HC) diet during gestation and lactation, and measured metabolic phenotypes between birth and 10 months of age in male offspring. Perinatal HP/LC and LP/HC exposures resulted in a decreased ability to clear glucose in the offspring, with reduced baseline insulin and glucose concentrations in the LP/HC group and a reduced insulin response post-glucose challenge in the HP/LC group. The LP/HC diet group also showed reduced birth and weanling weights, whereas the HP/LC offspring displayed increased weanling weight with increased adiposity beyond 5 months of age. Gene expression profiling of hypothalamus and liver revealed alterations in diverse molecular pathways by both diets. Specifically, hypothalamic transcriptome and pathway analyses demonstrated perturbations of MAPK and hedgehog signaling, processes associated with neural restructuring and transmission, and phosphate metabolism by perinatal protein imbalances. Liver transcriptomics revealed changes in purine and phosphate metabolism, hedgehog signaling, and circadian rhythm pathways. Our results indicate maternal protein imbalances perturbing molecular pathways in central and peripheral metabolic tissues, thereby predisposing the male offspring to metabolic dysfunctions.
| S-EPMC6297185 | biostudies-literature
Project description:Maternal effects are an important evolutionary force that may either facilitate adaptation to a new environment or buffer against unfavourable conditions. The degree of variation in traits expressed by siblings from different mothers is often sensitive to environmental conditions. This could generate a Maternal-by-Environment interaction (M × E) that inflates estimates of Genotype-by-Environment effects (G × E). We aimed to test for environment-specific maternal effects (M × E) using a paternal full-sib/half-sib breeding design in the seed beetle Callosobruchus maculatus, where we split and reared offspring from the same mother on two different bean host types-original and novel. Our quantitative genetic analysis indicated that maternal effects were very small on both host types for all the measured life-history traits. There was also little evidence that maternal oviposition preference for a particular host type predicted her offspring's performance on that host. Further, additive genetic variance for most traits was relatively high on both hosts. While there was higher heritability for offspring reared in the novel host, there was no evidence for G × Es, and most cross-host genetic correlations were positive. This suggests that offspring from the same family ranked similarly for performance on both host types. Our results point to a genetic basis of host adaptation in the seed beetle, rather than maternal effects. Even so, we encourage researchers to test for potential M × Es because, due to a lack of testing, it remains unclear how often they arise.
| S-EPMC8249602 | biostudies-literature