Impact of dioxin exposure and high fat diet feeding on adult mouse islets
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE144765 | GEO | 2020/10/05
REPOSITORIES: GEO
Similar Datasets
Project description:Impact of dioxin exposure and high fat diet feeding on adult mouse islets
| PRJNA604802 | ENA
Project description:Purpose: to determine whether exposure to chronic low dose dioxin impacts pancreas physiology during pregnancy (dams) and/or pancreas development (offspring)
2023-02-04 | GSE144793 | GEO
Project description:Dioxin-like chemicals are well-known for their ability to upregulate expression of numerous genes via the AH receptor (AHR). However, recent transcriptomic analyses in several laboratories indicate that dioxin-like chemicals or AHR genotype itself also can downregulate levels of mRNAs encoded by numerous genes. The mechanism responsible for such downregulation is unknown. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA levels in several systems, might be responsible for mRNA downregulation in dioxin/AHR pathways. We used the Ambion miRNA array platform as well as quantitative RT-PCR to measure miRNA levels in dioxin-sensitive Long-Evans (Turku/AB; L-E) rats vs. dioxin-resistant Han/Wistar(Kuopio; H/W) rats. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo caused no significant changes in miRNA levels in rat livers. AHR genotype had no effect on hepatic miRNA levels in response to TCDD – no miRNAs differed in expression between between L-E rats (that have wildtype AHR) compared to H/W rats (whose AHR has a large deletion in the transactivation domain). It is unlikely that mRNA downregulation by dioxins is mediated by miRNAs, nor are miRNAs likely to play a significant role in dioxin toxicity in adult rodent liver. Manuscript Submitted: Moffat ID, Boutros PC, Celius T, Pohjanvirta R & Okey AB. Micro-RNAs in rodent liver are refractory to dioxin treatment. Toxicological Sciences May, 2007. Keywords: miRNA expression, response to xenobiotics, genetic modification, comparative genome hybridization
2007-08-15 | GSE8467 | GEO
Project description:Dioxin is one of the most common historic industrial contaminants with several major industry and government accidents having exposed large numbers of the worldwide population over the past century. Previous rat studies have demonstrated the ability of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) exposure to promote the epigenetic transgenerational inheritance of disease susceptibility in subsequent generations. The types of disease observed include testis, ovary, kidney, prostate and obesity pathologies. The current study was designed to use an epigenome-wide association study (EWAS) to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. The transgenerational F3 generation dioxin lineage male rats with and without a specific disease were compared to identify differential DNA methylation regions (DMRs). The genomic features of the DMRs are characterized. Observations demonstrate that disease specific epimutation DMRs exist for the transgenerational dioxin lineage rats that can potentially be used as epigenetic biomarkers for testis, ovary, kidney, prostate and obesity diseases. These disease specific DMRs were associated with genes that have previously been shown to be linked with these diseases. This EWAS for transgenerational disease identified epigenetic biomarkers and provides the proof of concept of the potential to develop similar biomarkers for humans to diagnose disease susceptibilities and facilitate preventative medicine.
2020-12-02 | GSE157539 | GEO
Project description:Dioxin-like chemicals are well-known for their ability to upregulate expression of numerous genes via the AH receptor (AHR). However, recent transcriptomic analyses in several laboratories indicate that dioxin-like chemicals or AHR genotype itself also can downregulate levels of mRNAs encoded by numerous genes. The mechanism responsible for such downregulation is unknown. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA levels in several systems, might be responsible for mRNA downregulation in dioxin/AHR pathways. We used the Ambion miRNA array platform as well as quantitative RT-PCR to measure miRNA levels in dioxin-sensitive Long-Evans (Turku/AB; L-E) rats vs. dioxin-resistant Han/Wistar(Kuopio; H/W) rats. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo caused no significant changes in miRNA levels in rat livers. AHR genotype had no effect on hepatic miRNA levels in response to TCDD – no miRNAs differed in expression between between L-E rats (that have wildtype AHR) compared to H/W rats (whose AHR has a large deletion in the transactivation domain). It is unlikely that mRNA downregulation by dioxins is mediated by miRNAs, nor are miRNAs likely to play a significant role in dioxin toxicity in adult rodent liver. Manuscript Submitted: Moffat ID, Boutros PC, Celius T, Pohjanvirta R & Okey AB. Micro-RNAs in rodent liver are refractory to dioxin treatment. Toxicological Sciences May, 2007. Keywords: miRNA expression, response to xenobiotics, genetic modification, comparative genome hybridization In the dioxin-sensitive L-E rats we compared miRNA expression levels 19 h post-TCDD treatment vs. corn oil vehicle treatment. In the dioxin-resistant H/W rats we compared miRNA levels 19 h post-TCDD treatment vs.corn oil vehicle treatment.
2007-08-15 | E-GEOD-8467 | biostudies-arrayexpress
Project description:Purpose: Hyperinsulinemia and insulin resistance are co-existing characteristics of type 2 diabetes, whereas the forerunner initiating the deleterious cycle remains elusive. The temporal transcriptomic landscape of islets (responsible for hyperinsulinemia) and liver (involved in insulin resistance) could provide new insights. Methods: C57BL/6N mice were fed a 60% high-fat diet (HFD) or control diet (CD) for 24 weeks. RNA-sequencing of islet and liver samples were respectively performed in quadruplicates at six consecutive time points of diet treatments (week 4, 8, 12, 16, 20 and 24), using BGISEQ-500 sequencing platform by the Beijing Genomics Institute (Shenzhen, China).The sequencing raw reads were filtered for low-quality, adaptor-polluted, high content of unknown base reads by SOAPnuke (v1.5.2). We used Trinity (v2.0.6) to perform de novo assembly, and Tgicl (v2.0.6) on cluster transcripts to remove redundancy and get unigenes. The high-quality clean reads were then mapped to the mouse reference genome (GRCm38) via HISAT2 (v2.0.4) and full-length transcriptome database via Bowtie2 (v2.2.5). The gene expression levels were then quantified by RSEM (v1.1.12) and were normalized by the method of fragments per kilobase of exon model per million reads mapped (FPKM). To interpret the functional significance of differentially expressed genes (DEGs), pathway analyses was conducted to determine enriched canonical pathways. Results: Combined analyses of all 96 samples yielded the identification of 21990 annotated genes. Differentially expressed genes (DEGs) between the two groups (HFD vs. CD) at each time point were identified using the criteria of fold change ≥2 and adjusted P-value ≤0.05. In total, 3844 DEGs were found in islets, of which 33 were shared among all six time points. With regard to liver, 4101 DEGs were discovered throughout 24 weeks of feeding, of which 39 were overlapped. Our islet and liver RNA-sequencing datasets outlined the impact of HFD on dynamics of molecular network at different stages. Correlation analyses of islet and liver modules with metabolic phenotypes illustrated that these two tissues jointly program β-cell adaption to irreversible impairment. Top scored networks combining islet and liver transcriptomes showed potential interactions of genes implicated in cell cycle during week 4, organismal development around week 12, and immune cell trafficking at week 24. Conclusions: Our data provide a comprehensive landscape of crosstalk between islets and liver in diet-induced diabetes, linking to the development of islet dysfunction and insulin resistance.
2020-06-26 | GSE153222 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE15857: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Kidney GSE15858: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Liver Refer to individual Series
2010-05-05 | E-GEOD-15859 | biostudies-arrayexpress
Project description:We used microarrays to unveil the gene expression alterations upon short-term HFD administration We found that short-term HFD administration impacts hepatic lipid biosynthesis and redox status
2017-08-01 | GSE94867 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
2009-09-21 | GSE15858 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
2009-09-21 | GSE15857 | GEO