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Animal models of steatohepatitis.

Publication ,  Journal Article
Koteish, A; Mae Diehl, A
Published in: Best Pract Res Clin Gastroenterol
October 2002

Animal models of hepatic steatosis and steatohepatitis have improved our understanding of the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Three models, genetically obese ob/ob mice, lipoatrophic mice and normal rats fed choline-deficient, methionine-restricted diets, have been particularly informative. All support the multiple 'hit' hypothesis for NAFLD pathogenesis that suggests that fatty livers are unusually vulnerable to oxidants and develop steatohepatitis when secondary insults generate sufficient oxidants to cause liver cell death and inflammation. Steatohepatitis, in turn, increases sensitivity to other insults that induce hepatic fibrosis, promoting the evolution of cirrhosis. Early during NAFLD pathogenesis, inhibitor kappa kinase beta (IKKbeta), an enzyme that induces tumour necrosis factor alpha (TNFalpha) and other proinflammatory cytokines, is activated and this causes insulin resistance. Inhibition of IKKbeta or TNFalpha improves insulin sensitivity, steatosis and steatohepatitis in animals, suggesting novel strategies to prevent and treat early NAFLD in humans.

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Published In

Best Pract Res Clin Gastroenterol

DOI

ISSN

1521-6918

Publication Date

October 2002

Volume

16

Issue

5

Start / End Page

679 / 690

Location

Netherlands

Related Subject Headings

  • Rats, Zucker
  • Rats
  • Oxidative Stress
  • Oxidation-Reduction
  • Mice, Transgenic
  • Mice, Obese
  • Mice
  • Leptin
  • Insulin Resistance
  • Gastroenterology & Hepatology
 

Citation

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Koteish, A., & Mae Diehl, A. (2002). Animal models of steatohepatitis. Best Pract Res Clin Gastroenterol, 16(5), 679–690. https://doi.org/10.1053/bega.2002.0332
Koteish, Ayman, and Anna Mae Diehl. “Animal models of steatohepatitis.Best Pract Res Clin Gastroenterol 16, no. 5 (October 2002): 679–90. https://doi.org/10.1053/bega.2002.0332.
Koteish A, Mae Diehl A. Animal models of steatohepatitis. Best Pract Res Clin Gastroenterol. 2002 Oct;16(5):679–90.
Koteish, Ayman, and Anna Mae Diehl. “Animal models of steatohepatitis.Best Pract Res Clin Gastroenterol, vol. 16, no. 5, Oct. 2002, pp. 679–90. Pubmed, doi:10.1053/bega.2002.0332.
Koteish A, Mae Diehl A. Animal models of steatohepatitis. Best Pract Res Clin Gastroenterol. 2002 Oct;16(5):679–690.
Journal cover image

Published In

Best Pract Res Clin Gastroenterol

DOI

ISSN

1521-6918

Publication Date

October 2002

Volume

16

Issue

5

Start / End Page

679 / 690

Location

Netherlands

Related Subject Headings

  • Rats, Zucker
  • Rats
  • Oxidative Stress
  • Oxidation-Reduction
  • Mice, Transgenic
  • Mice, Obese
  • Mice
  • Leptin
  • Insulin Resistance
  • Gastroenterology & Hepatology