The hepatic methylome of liver-specific insulin receptor knockout (LIRKO) mouse offspring
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ABSTRACT:
PROVIDER: PRJNA593236 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10582312.fastq.gz | Fastqsanger.gz | |||
| SRR10582313.fastq.gz | Fastqsanger.gz | |||
| SRR10582314.fastq.gz | Fastqsanger.gz | |||
| SRR10582315.fastq.gz | Fastqsanger.gz | |||
| SRR10582316.fastq.gz | Fastqsanger.gz |
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Project description:Liver-specific insulin receptor knockout (LIRKO) mouse is a unique non-dietary model of insulin resistant, hyperglycemia, dyslipidemia and atherosclerosis that resembles several clinical features of the human metabolic syndrome. By enhanced reduced representation bisulfite sequencing (ERRBS) analysis of the livers of wild-type (WT) offspring of LIRKO mice, we identified that genes with differential DNA methylation were enriched for cholesterol synthesis, MAPK, AKT, insulin and TGF-β signaling, including the NREP and GDF15.
2021-01-04 | GSE141379 | GEO
Project description:At 2 months of age, liver-specific insulin receptor knockout (LIRKO) mice present hyperglycemia and hyperinsulinemia. Furthermore, LIRKO mice have increased levels of hepatic cholesterol. Indeed, many changes seen in cholesterol metabolism in LIRKO mice are also observed in humans with metabolic syndrome. For example, both show decreased levels of HDL and increased secretion of apoB and VLDL. These findings make the LIRKO mouse a unique non-dietary model of insulin resistant, hyperglycemia, dyslipidemia and atherosclerosis that resembles several clinical features of the human metabolic syndrome. By hepatic transcriptomic analysis of the wild-type (WT) offspring of LIRKO mice, we identify that members of the TGF-β family are differentially expressed in the offspring, including the NREP and GDF15.
2021-01-04 | GSE141077 | GEO
Project description:The hepatic transcriptome of liver-specific insulin receptor knockout (LIRKO) mouse offspring
| PRJNA591946 | ENA
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:Background: Assisted Reproductive Technologies (ART) - treatments to allow parenthood to couples facing fertility issues- have allowed the birth of > 5 million babies worldwide. Notwithstanding most of ART children are healthy at birth, several studies reported that ART may affect early-life experience causing permanent changes in fetal programming and, consequently, leading to increased predisposition to metabolic disorders in adulthood. Currently, the metabolic health status of ART children has been poorly investigated and it will take decades before large-scale population studies will be implemented. Studies on animal models indicated impaired in utero development of ART conceptuses. Relevantly, our preliminary data showed hypomethylation of liver from ART foetuses, which may contribute to the fetal programming of adult diseases. Regarding adult ART offspring, obesity, glucose intolerance and lipid accumulation in the liver have been previously described in mouse model, indicative of increased risk to develop metabolic disorders. However, little is known on the pathophysiological mechanism behind the metabolic abnormalities in ART offspring. In this context, this study investigated the influence of ART on the function of the liver, a major organ involved in the maintenance of metabolic homeostasis.
Methods: To assess the influence of ART on liver functions, proteomic analysis was carried out on adult liver from 4 months old offspring developed following Embryo Transfer (ET), in vitro culture (IVC) and blastomere biopsy (BB). Control (CTR) consisted of naturally conceived offspring. Then, to verify whether and how changes in liver proteome were associated with perturbation of the metabolic status of adult offspring, general growth and physiological parameters (e.g. glucose tolerance, insulin resistance, plasmatic levels of interleukin 6, triglycerides and total cholesterol) were assessed.
Results: Proteomic analysis of adult liver showed deregulated expression of proteins involved in lipid, carbohydrate and energy metabolism as well as cellular processes in adult offspring developed following BB, IVC and ET. Characterization of metabolic phenotype of adult offspring revealed increased body weight in ART offspring, glucose intolerance in BB, IVC, ET males and BB females, insulin resistance on BB offspring, low plasmatic level of Interleukin-6 in BB, IVC, ET males and high level of triglycerides and total cholesterol in BB females vs CTR which are phenotypic manifestation of liver disfunctions and core symptoms of metabolic syndrome.
Conclusion: Our study showed DE of proteins involved in metabolic and cellular processes, indicative of impaired hepatic functions which may contribute to the onset and progression of various diseases (e.g. NASH, NAFLD, hepatocarcinoma) in mouse offspring developed following ART. Moreover, impaired hepatic metabolism was associated with obesity, glucose intolerance, insulin resistance and dyslipidaemia which are core symptoms of metabolic syndrome and risk factor for diabetes and cardiovascular diseases in adult ART offspring. Thus, we provide evidence of Assisted Reproductive Technologies is a risk factor for perturbation of hepatic proteome, associated with the increased predisposition to liver diseases and metabolic syndrome in adulthood.
2020-05-14 | MSV000085413 | MassIVE
Project description:Paternal nicotine exposure can alter phenotypes in future generations. To explore whether paternal nicotine exposure affects the hepatic repair to chronic injury which would lead to hepatic fibrosis in offspring, we establish a paternal effect model based on nicotine exposure in mice.
2020-07-31 | GSE155308 | GEO
Project description:We determined the effects of excess folic acid supplementation (5x recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of gestational dibetes (GDM; 45% kcal fat diet) and control mice (10% kcal diet) we show that folic acid supplementation increased weight gain and fat mass in both GDM and control mice but improved insulin sensitivity in GDM mice and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation may not be due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (GDM and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the offspring from supplemented dams but this differed between GDM and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype, and has sex-specific effects on offspring pancreas and liver.
2023-09-29 | GSE237149 | GEO
Project description:Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother Male offspring showed features of metabolic syndrome after receiving a high fat diet, regardless of the diet of the dam. Glucose and lipid metabolism in male offspring was unaltered. Insulin sensitivity and hepatic fatty acid storage in female offspring of low-protein-fed dams changed in such a way that it resembled the male pattern of insulin sensitivity and hepatic fatty acid storage. Microarray analysis on hepatic gene expression patterns confirmed these findings. We therefore conclude that in mice, maternal protein restriction does not change the response of glucose and fatty acid metabolism to a high fat diet in male offspring, but does program metabolism in female offspring in such a way that it resembles male metabolism. Our findings might have implications for potential future gender-specific treatment of the features of metabolic diseases. Total RNA obtained from liver (16 samples per gender) were compared in the different groups. In total, 4 groups per gender, each group consisting of 4 biological replicates.
2012-02-08 | E-GEOD-15940 | biostudies-arrayexpress
Project description:Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother Male offspring showed features of metabolic syndrome after receiving a high fat diet, regardless of the diet of the dam. Glucose and lipid metabolism in male offspring was unaltered. Insulin sensitivity and hepatic fatty acid storage in female offspring of low-protein-fed dams changed in such a way that it resembled the male pattern of insulin sensitivity and hepatic fatty acid storage. Microarray analysis on hepatic gene expression patterns confirmed these findings. We therefore conclude that in mice, maternal protein restriction does not change the response of glucose and fatty acid metabolism to a high fat diet in male offspring, but does program metabolism in female offspring in such a way that it resembles male metabolism. Our findings might have implications for potential future gender-specific treatment of the features of metabolic diseases.
2012-02-08 | GSE15940 | GEO