Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis.
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.
Department of Internal Medicine I, University of Bonn, Germany.
Robert
R
Schierwagen
Department of Internal Medicine I, University of Bonn, Germany.
Lara
L
Maybüchen
Department of Internal Medicine II, University of Bonn, Germany.
Sebastian
S
Zimmer
Institute of Pathology, University of Bonn, Germany.
Kanishka
K
Hittatiya
Department of Internal Medicine III, RWTH University of Aachen, Germany.
Christer
C
Bäck
Department of Internal Medicine I, University of Bonn, Germany.
Sabine
S
Klein
Department of Internal Medicine I, University of Bonn, Germany.
Frank E
FE
Uschner
Department of Internal Medicine I, University of Bonn, Germany.
Winfried
W
Reul
1] Division of Nephrology, RWTH University of Aachen, Germany [2] Institute of Pathology, RWTH University of Aachen, Germany.
Peter
P
Boor
Department of Internal Medicine II, University of Bonn, Germany.
Georg
G
Nickenig
Department of Internal Medicine I, University of Bonn, Germany.
Christian P
CP
Strassburg
Department of Internal Medicine III, RWTH University of Aachen, Germany.
Christian
C
Trautwein
Department of Human Biology, University of Maastricht, Netherlands.
Jogchum
J
Plat
Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Germany.
Dieter
D
Lütjohann
Department of Internal Medicine I, University of Bonn, Germany.
Tilman
T
Sauerbruch
Department of Internal Medicine III, RWTH University of Aachen, Germany.
Frank
F
Tacke
Department of Internal Medicine I, University of Bonn, Germany.
Jonel
J
Trebicka
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D066273:Diet, Western / Q000009:adverse effects*; D006975:Hypertension, Portal / Q000209:etiology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000209:etiology*; D024821:Metabolic Syndrome / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology*
D001057:Apolipoproteins E