Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

A preclinical mouse model of nonalcoholic steatohepatitis and hepatocellular cancer that mimics human disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Yujin Hoshida

PROVIDER: E-GEOD-67680 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer.

Asgharpour Amon A Cazanave Sophie C SC Pacana Tommy T Seneshaw Mulugeta M Vincent Robert R Banini Bubu A BA Kumar Divya Prasanna DP Daita Kalyani K Min Hae-Ki HK Mirshahi Faridoddin F Bedossa Pierre P Sun Xiaochen X Hoshida Yujin Y Koduru Srinivas V SV Contaifer Daniel D Warncke Urszula Osinska UO Wijesinghe Dayanjan S DS Sanyal Arun J AJ

Journal of hepatology 20160531 3

<h4>Background & aims</h4>The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development.<h4>Methods</h4>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.<h4>Results</h4>Following initiation o ...[more]

PMID: 27261415

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Project description:Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPARM-NM-1 target genes. The aim of this study was to investigate the role of PPARM-NM-1 in heme-induced hyperproliferation and hyperplasia. Male PPARM-NM-1 KO and WT mice received a purified diet with or without heme. As PPARM-NM-1 is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPARM-NM-1 leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPARM-NM-1 in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPARM-NM-1 KO mice. We conclude that PPARM-NM-1 plays a protective role in colon against oxidative stress, but PPARM-NM-1 does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia. Wild type and peroxisome proliferator-activated receptor alpha (PPARM-NM-1) knockout mice were fed a Westernized high fat diet, or the same diet supplemented with 0.5 M-BM-5mol heme/g diet. After 14 days of intervention, mice were killed and gene expression was profiled in colon.

Dataset Information

A preclinical mouse model of nonalcoholic steatohepatitis and hepatocellular cancer that mimics human disease

Publications

A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer.

Similar Datasets

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