Non-
alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis,
inflammation and
fibrosis, which might progress to
cirrhosis. Human NASH is associated with
metabolic syndrome (MS). Currently, rodent NASH models either lack significant
fibrosis or MS.
ApoE(-/-) mice are a MS model used in cardiovascular research. The aim of this work was to establish and characterise a novel mouse NASH model with significant
fibrosis and MS.
ApoE(-/-) and wild-type mice (wt) were fed either a western-diet (WD),
methionine-
choline-deficient-diet (MCD) or normal chow. Liver histology, RT-PCR, hepatic
hydroxyproline content,
triglycerides and
cholesterol levels, and fasting
glucose levels assessed hepatic steatosis,
inflammation and
fibrosis. Further, portal pressure was measured invasively, and kidney pathology was assessed by histology.
ApoE(-/-) mice receiving WD showed abnormal
glucose tolerance,
hepatomegaly,
weight gain and full spectrum of NASH including hepatic steatosis,
fibrosis and
inflammation, with no sign of renal damage. MCD-animals showed less severe
liver fibrosis, but detectable renal pathological changes, besides
weight loss and unchanged
glucose tolerance. This study describes a murine NASH model with distinct hepatic steatosis,
inflammation and
fibrosis, without renal pathology.
ApoE(-/-) mice receiving WD represent a novel and fast model with all characteristic features of NASH and MS well suitable for NASH research.