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Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis

Transgenic liver-specific inactivation of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) impairs hepatic insulin clearance and causes hyperinsulinemia, insulin resistance, elevation in hepatic and serum triglyceride levels, and visceral obesity. It also predisposes to nonalcho...

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Autores principales: Ghosh, Sumona, Kaw, Meenakshi, Patel, Payal R, Ledford, Kelly J, Bowman, Thomas A, McInerney, Marcia F, Erickson, Sandra K, Bourey, Raymond E, Najjar, Sonia M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177946/
https://www.ncbi.nlm.nih.gov/pubmed/21949477
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author Ghosh, Sumona
Kaw, Meenakshi
Patel, Payal R
Ledford, Kelly J
Bowman, Thomas A
McInerney, Marcia F
Erickson, Sandra K
Bourey, Raymond E
Najjar, Sonia M
author_facet Ghosh, Sumona
Kaw, Meenakshi
Patel, Payal R
Ledford, Kelly J
Bowman, Thomas A
McInerney, Marcia F
Erickson, Sandra K
Bourey, Raymond E
Najjar, Sonia M
author_sort Ghosh, Sumona
collection PubMed
description Transgenic liver-specific inactivation of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) impairs hepatic insulin clearance and causes hyperinsulinemia, 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.
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spelling pubmed-31779462011-09-21 Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis Ghosh, Sumona Kaw, Meenakshi Patel, Payal R Ledford, Kelly J Bowman, Thomas A McInerney, Marcia F Erickson, Sandra K Bourey, Raymond E Najjar, Sonia M Hepat Med Original Research Transgenic liver-specific inactivation of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) impairs hepatic insulin clearance and causes hyperinsulinemia, 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. Dove Medical Press 2010-05-31 /pmc/articles/PMC3177946/ /pubmed/21949477 Text en © 2010 Ghosh et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Ghosh, Sumona
Kaw, Meenakshi
Patel, Payal R
Ledford, Kelly J
Bowman, Thomas A
McInerney, Marcia F
Erickson, Sandra K
Bourey, Raymond E
Najjar, Sonia M
Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis
title Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis
title_full Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis
title_fullStr Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis
title_full_unstemmed Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis
title_short Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis
title_sort mice with null mutation of ceacam1 develop nonalcoholic steatohepatitis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177946/
https://www.ncbi.nlm.nih.gov/pubmed/21949477
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