title: A mouse model for nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of the growing metabolic syndrome epidemic that could progress to cirrhosis. Animal models adequately mimicking this condition in humans are scanty.
  
  
  OBJECTIVE
  The objective of our study was to investigate whether high-fat diets (HFD) with adequate methionine and choline levels can induce pathophysiological features typical of human NASH in C57BL/6J mice.
  
  
  METHODS
  Forty C57BL/6J mice, divided into control and high-fat (HF) groups, were fed low-fat diet and HFD, ad libitum respectively for 20 weeks. At the end of 20 weeks, animals were sacrificed and assays were performed for blood biomarkers typical of human NASH. Adipose tissue depots were collected and liver samples were processed for histological examination.
  
  
  RESULTS
  High-fat feeding led to increased triglyceride accumulation in the liver (8.9 μmol/100 mg liver tissue vs. 2.6 μmol/100 mg for control) and induced histopathological features of human NASH including hepatic steatosis, ballooning inflammation and fibrosis. Expressions of proteins and chemokines predominant in NASH including collagens I, III and IV and platelet derived growth factor (PDGF) A and B were significantly higher in animals fed the HFD. Liver enzymes alanine transaminase, aspartate transaminase and alkaline phosphatase were significantly (P<.05) elevated in the HF group compared to controls. Mice on HFD also developed hyperglycemia, hyperinsulinemia, hypoadiponectinemia along with elevated tumor necrosis factor α, resistin, leptin, free fatty acids, transforming growth factor β and malondialdehyde levels that characterize NASH in humans.
  
  
  CONCLUSIONS
  Long-term HF feeding with adequate methionine and choline can induce many of the pathophysiological features typical of human NASH in C57BL/6J mice.
authors.affiliation: Department of Nutrition and Food Sciences, Texas Woman's University, Denton, USA. ssundare@dom.wustl.edu
authors.forename: Sinju
authors.initials: S
authors.lastname: Sundaresan
authors.forename: Parakat
authors.initials: P
authors.lastname: Vijayagopal
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Mills
authors.forename: Vicky
authors.initials: V
authors.lastname: Imrhan
authors.forename: Chandan
authors.initials: C
authors.lastname: Prasad
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease