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Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα [array]

ABSTRACT: Comparison of gene expression in livers of either WT mice or mice with hepatic specific deletion of the gene Tribbles1. Animal groups were both Trib1 cKO mice homozygous for a floxed allele of Trib1. Mice aged 8-10 weeks were treated with adeno associated virus (AAV) encoding Cre recombinase (AAV_Cre) or no gene (AAV_null). The WT group is mice treated with AAV_Null, the liver-specific KO group treated with AAV_Cre. Gene expression data was then used in Ingenuity Pathway analysis to attempt to identify upstream transcription factors that might be responsible for the gene expression changes observed.

ORGANISM(S): Mus musculus

PROVIDER: GSE70846 | GEO | 2015/07/14

SECONDARY ACCESSION(S): PRJNA289681

REPOSITORIES: GEO

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Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα [array]

Project description:Comparison of gene expression in livers of either WT mice or mice with hepatic specific deletion of the gene Tribbles1. Animal groups were both Trib1 cKO mice homozygous for a floxed allele of Trib1. Mice aged 8-10 weeks were treated with adeno associated virus (AAV) encoding Cre recombinase (AAV_Cre) or no gene (AAV_null). The WT group is mice treated with AAV_Null, the liver-specific KO group treated with AAV_Cre. Gene expression data was then used in Ingenuity Pathway analysis to attempt to identify upstream transcription factors that might be responsible for the gene expression changes observed. All animals were 8-10 weeks of age, and all animals were homozygous for the floxed allele of Trib1. WT animals were treated with AAV_Null, Trib1 liver specific KO mice were treated with AAV_Cre. Mice were euthanized at 1-week post injection of AAV, and RNA collected from whole liver tissue.

2015-07-14 | E-GEOD-70846 | biostudies-arrayexpress

Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα [ChIP-Seq]

2015-07-14 | GSE70716 | GEO

Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBP? [ChIP-Seq]

Project description:We report ChIP-Seq data for C/EBPa in livers of mice with liver-specific KO (LSKO) of Trib1 as compared to WT controls, or in livers of mice overexpressing C/EBPa via adeno-associated virus (AAV) as compared to controls. 8-10 week old Trib1 flox/flox mice treated with AAV_Null (WT) or AAV_Cre (LSKO); 8-10 week old C57B/6 WT mice treated with AAV_Null or AAV_Cebpa.

2015-07-14 | E-GEOD-70716 | biostudies-arrayexpress

Long-term liver expression of an apolipoprotein A-I mimetic peptide attenuates IFNα-induced inflammation and promotes antiviral activity

Project description:Apolipoprotein A-I mimetic peptides are amphipathic alpha-helix peptides that display similar functions to apolipoprotein A-I. Preclinical and clinical studies have demonstrated the safety and efficacy of apolipoprotein A-I mimetic peptides in multiple indications associated with inflammatory processes. In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.

2021-09-09 | PXD023281 | Pride

transcriptional profiling of brain from WT, AAV9-Ids or Null-treated MPSII mice.

Project description:The experiment evaluates the therapeutic effect brain injected AAV9-IDS (Adeno-associated virus 9 encoding IDS enzyme) treatment in a mouse model of Mucopolysaccharidosis Type II (MPSII). Microarrays were performed in order to compare the transcriptional profiling after the treatment. Three groups were analyzed, wild type (WT) mice, MPSII mice treated with AAV-NULL (AAV vector alone) and MPSII mice treated with AAV-IDS (vector encoding IDS enzyme). Four months after vector administration (at 6 months of age), animals were sacrificed and tissues were harvested and processed. RNA isolated from the encephalon of three groups of mice was analysed using the Affimetrix® microarray platform

2019-05-20 | E-MTAB-4728 | biostudies-arrayexpress

Gene expression profiling of HDAC3-depleted mouse liver rescued with wild-type exogenous HDAC3

Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers. 4-months old C57BL/6 male mice were co-injected with AAV-Cre or AAV-Cre plus AAV-Flag-HDAC3. Mice were fed ad libitum and harvested at 5 pm (ZT10) at 2-weeks post-injection. Liver total RNA was extracted and hybridized to Affymetrix Mouse Gene 1.0ST array.

2013-11-25 | E-GEOD-49386 | biostudies-arrayexpress

Gene expression profiling of HDAC3-depleted mouse liver rescued with wild-type exogenous HDAC3

2013-11-25 | GSE49386 | GEO

Functional characterization of hGRÎ² Isoform in mouse liver

Project description:We used AAV as a vector to deliver hGRÎ² to C57BL/6 mouse liver. We collected liver samples for microarray analysis to investigate any phenotype as well as the underlying specific signaling pathway. In particular, we would like to determine if and how hGRÎ² overexpression in liver affects mGRÎ±âs gene transcription profile in C57BL/6 mice. Three replicates for each group: untreated WT liver, AAV-GFP treated liver, and AAV-hGRB treated liver.

2015-12-11 | E-GEOD-75740 | biostudies-arrayexpress

Apolipoprotein A-I mimetic peptide L37pA attenuates IFNα-induced inflamation and promotes antiviral activity

Project description:Apolipoprotein A-I mimetic peptides are amphipathic alpha helix peptides that display similar functions to apolipoprotein A-I, and preclinical studies have evaluated . In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.

2020-12-08 | GSE162764 | GEO

Notum promotes thermogenesis and protects against diet-induced obesity and insulin resistance in mice

Project description:Notum is a liver-secreted inhibitor of Wnt signaling pathway, which protected against diet induced obesity and improved glucose homeostasis when overexpressed in the mouse liver. Adeno-associated virus (AAV) vectors were used to overexpress green fluorescent protein (GFP) or Notum in the livers of male C57BL/6J mice maintained on a chow diet. Four weeks after the AAV injection, inguinal white adipose tissue (WAT) of these mice were collected to study Notum’s effect on gene expression. RNA-seq analysis of inguinal WAT collected from these mice revealed a highly significant enrichment of extracellular matrix (ECM) gene set among the down-regulated genes in the AAV-Notum group as compared to the AAV-GFP group. These data suggest that Notum inhibits WAT fibrosis, which may be one of the mechanisms by which Notum improves glucose homeostasis.

2021-08-24 | GSE148894 | GEO

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