Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fat-specific protein 27/CIDEC plays an important role in promoting alcoholic liver injury in mice and humans

ABSTRACT: Here, we developed a mouse model with long-term chronic (8-12 week) plus single/multiple binge ethanol feeding, which mimicks the drinking patterns of AH patients, who often have a history of chronic drinking plus recent excessive drinking. This model produces severe macrosteatosis, significant inflammation, and mild fibrosis. Moreover, we conducted translational studies by comparing transcriptome data from this clinically relevant in vivo model and human AH biopsy samples, and identified many similar disregulated genes in this animal model and AH samples. And we find that FSP27/CIDE-C plays a critical role in promoting steatosis and hepatocellular damage in mouse and in human AH.

ORGANISM(S): Mus musculus

PROVIDER: GSE67546 | GEO | 2016/11/21

SECONDARY ACCESSION(S): PRJNA280222

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Pyroptosis by Caspase11/4-Gasdermin-D Pathway in Alcoholic Hepatitis

Project description:Alcoholic hepatitis (AH) continues to be a disease with high mortality and no efficacious medical treatment. Although severe AH is presented as acute on chronic liver failure, what underlies this transition from chronic alcoholic steatohepatitis (ASH) to AH, is largely unknown. To address this question, unbiased RNA-seq and proteomic analyses were performed on livers of the recently developed AH mouse model which exhibits the shift to AH from chronic ASH upon weekly alcohol binge, and these results are compared with gene expression profiling data from AH patients. This cross-analysis has identified Casp11 (CASP4 in man) as a commonly upregulated gene known to be involved in non-canonical inflammasome pathway. Immunoblotting confirms CASP11/4 activation in AH mice but not in chronic ASH. Gasdermin-D (GSDMD) which induces pyroptosis (lytic cell death caused by bacterial infection) downstream of CASP11/4 activation, is also activated in AH livers. CASP11 deficiency reduces GSDMD activation, bacterial load in the liver, and the severity of AH. Conversely, the deficiency of IL-18, the key anti-microbial cytokine, aggravates hepatic bacterial load, GSDMD activation, and AH. Further, hepatocyte-specific expression of constitutively active GSDMD worsens hepatocellular lytic death and PMN inflammation. These results implicate pyroptosis induced by CASP11/4-GSDMD pathway in the pathogenesis of AH.

2017-03-31 | GSE97234 | GEO

A novel model of binge ethanol exposure reveals enhanced neurodegeneration with advanced age

Project description:Binge drinking is rising among aged adults (>65 years of age). The distinct effects of binge ethanol exposure on neurodegeneration in the aged brain are not well described. Using our model of intermittent binge ethanol exposure in young and aged mice, we investigated how binge ethanol expoure may promote neurodegenerative diease development. Spatial transcriptomics revealed that binge ethanol exposure enriched neurodegenerative disease pathways in the aged hippocampus, including tau hyperphosphorylation and neuronal death. These data suggest binge drinking during advanced aging may promote neurodegenerative disease development.

2024-03-18 | GSE236787 | GEO

Chronic, Chemogenetic Stimulation of The Nucleus Accumbens Produces Lasting Effects on Binge Drinking and Ameliorates Alcohol-Related Transcriptional and Morphological Changes

Project description:We report RNA-Seq data obtained from nucleus accumbens tissue of HDID-1 mice subjected to chronic stimulation via CNO/DREADDs within a Drinking in The Dark (DID) Paradigm. Here, we found that chronically increasing NAc activity (via CNO/hM3Dq) decreased binge-like drinking, an effect lasting for at least 7 days . CNO did not alter intake in hM4Di- or GFP-expressing mice. We observed interesting and significant changes in expression of several plasticity-related genes (e.g. Hdac4 was increased with binge drinking, and ameliorated with CNO).

2019-06-21 | GSE133115 | GEO

Next-generation sequencing (NGS) facilitates quantitative analysis of differentially expressed genes in ethanol-fed murine livers after ethanol binge

Project description:Purpose: The goals of this study are to use NGS-derived liver transcriptome profiling (RNA-seq) and identify differentially expressed genes in damaged livers that were exposed to 5% ethanol-containing liquid diet and ethanol binge. Methods: Liver mRNA profiles were generated from chronic ethanol feeding plus a single binge by deep sequencing, in duplicate, using Illumina Hiseq2500. qRT–PCR validation was performed using SYBR Green assay. Results: Chronic ethanol feeding plus a single binge treatment was associated with 422 downregulated genes and 384 upregulated genes, whereas Yap1 null livers had 351 downregulated genes and 287 upregulated genes after ethanol/CCl4 induced liver damage. Conclusions: This study provides detailed analysis of liver transcriptomes during hepatocyte damage caused by chronic ethanol feeding plus a single binge treatment, with biologic replicates, generated by RNA-seq technology.

2022-02-10 | GSE196314 | GEO

Hepatic CYP2B10 is highly induced by binge ethanol and contributes to acute-on-chronic alcohol-induced liver injury

Project description:We altered the NIAAA (Gao Binge Model) of 8 week chronic plus binge ethanol (E8G1) to have 3 total ethanol gavages (5 g/kg; 1 every 24h) of ethanol after 8 weeks of chronic ethanol feeding (E8G3) to determine how the liver responds to chronic plus consecutive binge ethanol. Surprisingly, E8G3 treatment induced lower levels of liver injury, steatosis, inflammation, and fibrosis as compared to mice after E8G1 treatment. Microarray analyses were performed, identifying several pathways that may contribute to the observed liver adaptation to binge ethanol. In addition, cytochrome P450 2B10 (Cyp2b10) was a top upregulated gene in the E8G1 group and further upregulated in the E8G3 group, but only moderately induced after chronic ethanol consumption, which was confirmed by RT-qPCR and western blot analyses. Genetic disruption of the Cyp2b10 gene worsened liver injury in E8G1 and E8G3 mice with higher blood ethanol levels compared to wild-type control mice, while in vitro experimentation revealed that CYP2b10 did not directly promote ethanol metabolism. Metabolomic analyses revealed significant differences in hepatic metabolites from E8G1-treated Cyp2b10 KO and WT mice, and these metabolic alterations may contribute to the reduced liver injury in Cyp2b10 KO mice.

2022-09-07 | GSE212755 | GEO

Brain gene expression data from High Drinking in the Dark (HDID) and HS/Npt control mice

Project description:Alcohol Use Disorder (AUD) is a complex psychiatric disorder with strong genetic as well as environmental risk factors. One risk factor for developing AUD is binge drinking. High Drinking in the Dark mice (HDID-1) have been selectively bred from genetically heterogeneous mice (HS/Npt stock) for attaining high blood alcohol concentrations (BAC) after a 4-hour drinking session in which a single bottle containing 20% ethanol is available and serve as a genetic model of binge drinking. To discover molecular mechanisms underlying the genetic predisposition to binge drinking, we characterized global gene expression in 7 brain regions across the addiction neurocircuit, precisely excised using laser capture microdissection from male, ethanol-naive HDID-1 and control mice Brain regions included in the analysis are prefrontal cortex (PFC), nucleus accumbens core (AcbC), nucleus accumbens shell (AcbSh), bed nucleus of the stria terminalis (BNST), basolateral amygdala (BLA), central amygdala (CeA), and ventral tegmental area (VTA)

2017-01-10 | GSE93311 | GEO

Chronic alcohol drinking compromises lung immunity by altering immunometabolism in both human and mouse lungs

Project description:Heavy alcohol drinking dysregulates lung immunity and host defense, which makes individuals with AUD more susceptible to develop inflammatory condition in lungs with poor prognosis. Current study, we focused on exploring the effects of chronic alcohol consumption on lungs using NIAAA alcohol feeding model in mice with 10 days of a Lieber-DeCarli liquid diet containing 5% ethanol followed by a single ethanol binge (5 g/kg) and population based human lung transcriptome data from Genotype-Tissue Expression (GTEx) project consist of 328 alcohol drinkers and 110 non-drinkers. Flow cytometry and transcriptomics analysis in mice lungs revealed that alcohol consumption dysregulates cellularity of immune cell levels and lung immunity. Transcriptomics analysis both in lungs and liver at 9-, 24- hours and 14 days post ethanol binge in mice uncovered that the lungs were more sensitive to alcohol effect to down-regulate pathways of immune system regulations than liver. Comparative data analysis of lung transcriptomes between mice and human subjects not only confirmed similar dysregulation on lung immunity but also provided evidence that immunometabolic changes are the central driver of alterations in lung transcriptome with down regulating immune pathways and upregulating metabolic pathways. Since the NIAAA model recapitulates multiple changes in the lung transcriptome that had been observed in human subjects with chronic alcohol drinking, this makes the mouse model suitable for experimental studies exploring role of alcohol drinking in lung health. Chronic alcohol drinking reduced mTOR signaling and cellularity of immune cells, which can be further attenuated by selective inhibition of mTOR. BCAA-mTOR signaling axis can be an upstream regulator of alcohol induced dysregulation in lung immunity

2024-07-22 | GSE248233 | GEO

Chronic alcohol metabolism results in DNA repair infidelity and cell-cycle-induced senescence in neurons

Project description:Chronic and excessive binge-like drinking is a risk factor to pathological cognitive decline and dementia, but the mechanism underlying the prolonged and lasting effect of alcohol even in abstainers remains elusive. This study investigates how ethyl alcohol directly results in metabolic reprograming and persistent physiological changes in brain cells that underlies such effect.

2023-02-22 | GSE202183 | GEO

Effect of Chronic Ethanol Consumption in Rhesus Macaques on the Nucleus Accumbens Core Transcriptome

Project description:The current study was undertaken to expand on observations that transcriptome changes identified in the NAcc of Rhesus macaques underlies excessive ethanol consumption. Genome-wide RNA-Seq was used to examine the NAcc transcriptome in control, low/binge drinking and heavy/very heavy drinking animals. One key goal of the study was to determine if, as predicted and suggested by the epigenetic studies, excessive chronic ethanol consumption involves genes enriched in annotations associated with synaptic plasticity and specifically glutamate and GABA signaling plasticity.

2020-02-06 | GSE144783 | GEO