title: Mice with null mutation of Ceacam I develop nonalcoholic steatohepatitis.
abstract: Transgenic liver-specific inactivation of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) impairs hepatic insulin clearance and causes hyperinsuline-mia, insulin resistance, elevation in hepatic and serum triglyceride levels, and visceral obesity. It also predisposes to nonalchoholic steatohepatitis (NASH) in response to a high-fat diet. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we investigated whether Ceacam1 (gene encoding CEACAM1 protein) null mice with impaired insulin clearance also develop a NASH-like phenotype on a prolonged high-fat diet. Three-month-old male null and wild-type mice were fed a high-fat diet for 3 months and their NASH phenotype was examined. While high-fat feeding elevated hepatic triglyceride content in both strains of mice, it exacerbated macrosteatosis and caused NASH-characteristic fibrogenic changes and inflammatory responses more intensely in the null mouse. This demonstrates that CEACAM1-dependent insulin clearance pathways are linked with NASH pathogenesis.
authors.affiliation: Center for Diabetes and Endocrine Research, Toledo, OH, USA.
authors.forename: Sumona
authors.initials: S
authors.lastname: Ghosh
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Kaw
authors.forename: Payal R
authors.initials: PR
authors.lastname: Patel
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Ledford
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowman
authors.forename: Marcia F
authors.initials: MF
authors.lastname: McInerney
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Erickson
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Bourey
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar