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http://purl.uniprot.org/citations/18848945http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 causes hyperinsulinemia and insulin resistance, which result from impaired insulin clearance, in liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant mice (L-SACC1). These mice also develop steatosis. Because hepatic fat accumulation precedes hepatitis, lipid peroxidation, and apoptosis in the pathogenesis of nonalcoholic steatohepatitis (NASH), we investigated whether a high-fat diet, by causing inflammation, is sufficient to induce hepatitis and other features of NASH in L-SACC1 mice.

Methods

L-SACC1 and wild-type mice were placed on a high-fat diet for 3 months, then several biochemical and histologic analyses were performed to investigate the NASH phenotype.

Results

A high-fat diet caused hepatic macrosteatosis and hepatitis, characterized by increased hepatic tumor necrosis factor alpha levels and activation of the NF-kappaB pathway in L-SACC1 but not in wild-type mice. The high-fat diet also induced necrosis and apoptosis in the livers of the L-SACC1 mice. Insulin resistance in L-SACC1 fed a high-fat diet increased the hepatic procollagen protein level, suggesting a role in the development of fibrosis.

Conclusions

A high-fat diet induces key features of human NASH in insulin-resistant L-SACC1 mice, validating this model as a tool to study the molecular mechanisms of NASH."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2008.08.007"xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Heinrich G."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Najjar S.M."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Al-Share Q.Y."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Erickson S.K."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Fernstrom M.A."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Fedorova L."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"McInerney M.F."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Gatto-Weis C."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/author"Ledford K.J."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/name"Gastroenterology"xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/pages"2084-2095"xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/title"Development of nonalcoholic steatohepatitis in insulin-resistant liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant mice."xsd:string
http://purl.uniprot.org/citations/18848945http://purl.uniprot.org/core/volume"135"xsd:string
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