Bulk RNA sequencing of livers from Gubra-Amylin NASH diet fed Chrna2fl/fl and Chrna2fl/fl;Alb-Cre mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200595 | GEO | 2024/06/07
REPOSITORIES: GEO
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Project description:Bulk RNA sequencing of livers from Gubra-Amylin NASH diet fed Chrna2fl/fl and Chrna2fl/fl Alb-Cre mice
| PRJNA825497 | ENA
Project description:The etiology of non-alcoholic steatohepatitis (NASH) has been complicated. An increasing body of literature has indicated that hepatic oxidative stress exerts a causal role in driving NASH. Nevertheless, how the anti-oxidant defense system guards against oxidative stress and NASH remains unclear. In this study, we sought to investigate how the peroxidase peroxiredoxin 1 protects against NASH. To this end, we fed WT and hepatic PRDX1 knockout (Alb-Cre;Prdx1fl/fl) a methionine and choline deficient diet (MCD) for 5 weeks and collected liver samples for RNA sequencing analysis. As revealed by gene-set enrichment analysis (GSEA) and KEGG pathway enrichment analysis, there was an enrichment of genes involved in JAK-STAT signaling. Further, we observed that the expression of many genes involved in JAK-STAT signaling such as Pdgfb and Pdgfra was significantly increased in Alb-Cre;Prdx1fl/fl mice. Collectively, these results suggest that increased JAK-STAT signaling accounts for the deteriorated NASH phenotypes in Alb-Cre;Prdx1fl/fl mice.
2023-08-14 | GSE201030 | GEO
Project description:To investigate the alterlation of liver gene expression in diet-induced NASH model with adipose tissue insulin resistance, we evaluated liver of control mice and adipocyte-specific PDK1 knockout (PDK1KO) mice fed either normal chow(NC) or Gubra amylin NASH (GAN) diet for 16weeks after weaning at 4 weeks old. We then performed gene expression profiling analysis using data obtained from RNA-seq of these 4 groups.
2022-11-09 | GSE216128 | GEO
Project description:To investigate the alterlation of eWAT gene expression in diet-induced NASH model with adipose tissue insulin resistance, we evaluated eWAT of control mice and adipocyte-specific PDK1 knockout (PDK1KO) mice fed either normal chow(NC) or Gubra amylin NASH (GAN) diet for 16weeks after weaning at 4 weeks old. We then performed gene expression profiling analysis using data obtained from RNA-seq of these 4 groups.
2023-02-11 | GSE224733 | GEO
Project description:We applied RNA sequencing (RNA-seq) to study the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mouse model of NASH. GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16, or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls. We find that chow reversal promoted substantial benefits on metabolic, biochemical and histological outcomes accompanied by marked suppression of gene expression markers of hepatocellular senescence in GAN DIO-NASH mice. These therapeutic benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH.
2024-01-16 | GSE246328 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that can progress from simple fatty liver disease to non-alcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism and excretion (ADME) of drugs. Differential gene expression between three clinically defined pathological groups; normal, steatosis and NASH was analyzed. The samples were diagnosed as normal, steatotic, NASH with fatty liver (NASH fatty) and NASH without fatty liver (NASH NF). Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChipM-. Human 1.0ST arrays
2011-07-12 | E-MEXP-3291 | biostudies-arrayexpress
Project description:Non-alcoholic steatohepatitis (NASH) has emerged as a major challenge for public health because of high global prevalence and lack of evidence-based therapies. Most animal models of NASH lack sufficient validation regarding disease progression and pharmacological treatment. The Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mouse demonstrate clinical translatability with respect to disease etiology and hallmarks of NASH. This study aimed to evaluate disease progression and responsiveness to clinically effective interventions in GAN DIO-NASH mice. Disease phenotyping was performed in male C57BL/6J mice fed the GAN diet high in fat, fructose and cholesterol for 28-88 weeks. GAN DIO-NASH mice with biopsy-confirmed NASH and fibrosis received low-caloric dietary intervention, semaglutide (30 nmol/kg/day, s.c.) or lanifibranor (30 mg/kg/day, p.o.) for 8 and 12 weeks, respectively. Within-subject change in NAFLD Activity Score (NAS) and fibrosis stage was evaluated using automated deep learning-based image analysis. GAN DIO-NASH mice showed clear and reproducible progression in NASH, fibrosis stage and tumor burden with high incidence of hepatocellular carcinoma. Consistent with clinical trial outcomes, semaglutide and lanifibranor improved NAS, while only lanifibranor induced regression in fibrosis stage. Dietary intervention also demonstrated substantial benefits on metabolic outcomes and liver histology. Differential therapeutic efficacy of dietary intervention, semaglutide and lanifibranor was supported by quantitative histology, RNA sequencing, and blood/liver biochemistry. In conclusion, the GAN DIO-NASH mouse model recapitulates various histological stages of NASH and faithfully reproduces histological efficacy profiles of compounds in advanced clinical development for NASH. Collectively, these features highlight the utility of GAN DIO-NASH mice in preclinical drug development.
2022-02-21 | GSE196908 | GEO
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
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Project description:Loss of Chrna2 in the hepatocytes exacerbates the development of Metabolic dysfunction-associated steatohepatitis.
2024-06-07 | GSE264690 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease that ranges from simple steatosis, to inflammatory form non-alcoholic steatohepatitis (NASH), cirrhosis, and up to hepatocellular carcinoma. While NASH usually takes decades to develop at a rate of one stage per seven years, in the case of post-trasplant NASH (pt-NASH) develops fibrosis much more rapidly, with almost 50% of liver transplant recipients presenting stage 3 fibrosis by 5 years post-transplant. Archived fresh-frozen transplanted liver biopsy samples from four liver biopsy samples with evidence of NASH (2 recurrent and 2 de novo), two with simple steatosis (both de novo), and five with normal histology as controls had their transcriptome sequenced in two batches for deeper coverage.
2022-05-09 | E-MTAB-11688 | biostudies-arrayexpress