TY - JOUR
T1 - Animal models of steatohepatitis
AU - Koteish, Ayman
AU - Diehl, Anna Mae
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2002/10
Y1 - 2002/10
N2 - 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 (IKKβ), an enzyme that induces tumour necrosis factor alpha (TNFα) and other proinflammatory cytokines, is activated and this causes insulin resistance. Inhibition of IKKβ or TNFα improves insulin sensitivity, steatosis and steatohepatitis in animals, suggesting novel strategies to prevent and treat early NAFLD in humans.
AB - 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 (IKKβ), an enzyme that induces tumour necrosis factor alpha (TNFα) and other proinflammatory cytokines, is activated and this causes insulin resistance. Inhibition of IKKβ or TNFα improves insulin sensitivity, steatosis and steatohepatitis in animals, suggesting novel strategies to prevent and treat early NAFLD in humans.
KW - (TNFα)
KW - Inhibitor kappa kinase beta (IKKβ)
KW - Insulin resistance
KW - Oxidative stress
KW - Tumour necrosis factor alpha
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U2 - 10.1053/bega.2002.0332
DO - 10.1053/bega.2002.0332
M3 - Article
C2 - 12406439
AN - SCOPUS:0036782608
SN - 1521-6918
VL - 16
SP - 679
EP - 690
JO - Bailliere's Best Practice and Research in Clinical Gastroenterology
JF - Bailliere's Best Practice and Research in Clinical Gastroenterology
IS - 5
ER -