title: Nrf2 deletion causes "benign" simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease begins with the aberrant accumulation of triglyceride in the liver. Its spectrum includes the earliest stage of hepatic simple steatosis (SS), nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Generally, hepatic SS is often self-limited; however 10%-30% of patients with hepatic SS progress to NASH. The cause(s) of the transition from SS to NASH are unclear. We aimed to test the contribution of nuclear erythroid 2-related factor 2 (Nrf2) on the progression of "benign" SS to NASH in mice fed a high fat diet. In doing so, we discovered the influence of fatty acid in that progression.
  
  
  METHODS
  The involvement of Nrf2 in defending against the development of NASH was studied in an experimental model induced by a high-fat diet. Wild-type and Nrf2-null mice were fed the diet. Their specimens were analyzed for pathology as well as for fatty acid content and ratios.
  
  
  RESULTS
  In feeding the high-fat diet to the Wild-type and the Nrf2-null mice, the Wild-type mice increased hepatic fat deposition without inflammation or fibrosis (i.e., simple steatosis), while the Nrf2-null mice had significantly more hepatic steatosis and substantial inflammation, (i.e., nonalcoholic steatohepatitis). In addition, as a result of the high-fat diet, SFA (C20: 0, C22: 0) and MUFA (C18: 1, C20: 1) content in Nrf2-null mice were significantly higher than in Wild-type mice. In the Nrf2-null mice the PUFA/TFA ratio decreased; conversely, the MUFA/TFA ratio increased.
  
  
  CONCLUSIONS
  The deletion of Nrf2 causes "benign" SS to develop into NASH in mice fed with a high-fat diet, through prompt fatty acid accumulation and disruption of hepatic fatty acid composition in the liver.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wang
authors.forename: Yizhe
authors.initials: Y
authors.lastname: Cui
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shang
authors.initials: S
authors.lastname: Xu
authors.forename: Xiaochong
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Basic Veterinary Science, College of Veterinary Medicine Northeast Agricultural University, Harbin, Heilongjiang 150030, China. zhangxiuying@neau.edu.cn.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D015870:Gene Expression; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014280:Triglycerides