title: Effect of dietary fat to produce non-alcoholic fatty liver in the rat.
abstract: OBJECTIVE
  Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression.
  
  
  METHODS
  Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks.
  
  
  RESULTS
  Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups.
  
  
  CONCLUSIONS
  Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.
authors.affiliation: Physiology M311, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Umbreen
authors.initials: U
authors.lastname: Ahmed
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Redgrave
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Oates
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics; D004041:Dietary Fats / Q000009:adverse effects* / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain; D000071717:X-Box Binding Protein 1; D019014:fas Receptor / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002784:Cholesterol; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D006360:Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing); D015850:Interleukin-6; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D014280:Triglycerides; D000071717:X-Box Binding Protein 1; D019014:fas Receptor; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C000605545:Xbp1 protein, rat; C491523:Hmox1 protein, rat