Transcriptomics

Dataset Information

8

Gene expression profiles of livers and liver tumors from mice fed high-fat diet and high fructose-glucose solution for 52 weeks


ABSTRACT: The lack of a preclinical model of nonalcoholic steatohepatitis (NASH) and hepatocellular cancer (HCC) that recapitulates human disease is a major barrier to therapeutic development. We report a high fat-high sugar diet-induced NASH and HCC in a stable isogenic 129S1/SvImJ crossed with C57Bl/6J mice. Following diet initiation, there was sequential development of steatosis (4-8 weeks), steatohepatitis with ballooning and Mallory-Denk bodies (12-16 weeks), progressive fibrosis (16 week onwards) and spontaneous HCC (32-52 weeks). The mice developed obesity, insulin resistance and dyslipidemia. There was concordance with the human NASH transcriptome (FDR 0.001) with activation of lipogenic, inflammatory and apoptotic pathways relevant in humans. The HCC gene signature resembled S1 and S2 human HCC subclass (FDR 0.01 for both). This simple model of NASH and HCC that resembles human disease in terms of its triggers, physiological and biochemical parameters, histology, transcriptomic profile, and outcomes can facilitate preclinical development for these conditions. 129S1/SvImJ;C57Bl/6J (129/B6) mice were fed with high-fat diet (Western Diet) and high fructose-glucose solution (Sugar Water) (WD SW) or chow diet (CD) for 52 weeks, and total RNA samples were isolated from liver and tumor tissues for genome-wide expression profiling.

ORGANISM(S): Mus musculus  

SUBMITTER: Amon Asgharpour   Yujin Hoshida  Sophie C Cazanave  Arun J Sanyal 

PROVIDER: E-GEOD-67679 | ArrayExpress | 2016-07-25

SECONDARY ACCESSION(S): GSE67679PRJNA280622

REPOSITORIES: GEO, ArrayExpress

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The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development.A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains.Following initiation of the obesogenic diet, B6/129 mice developed obesity, insu  ...[more]

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