Effect of dietary fat to produce non-alcoholic fatty liver in the rat

J Gastroenterol Hepatol. 2009 Aug;24(8):1463-71. doi: 10.1111/j.1440-1746.2009.05870.x.


Background and aim: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis
  • Aspartate Aminotransferases / blood
  • Cholesterol / blood
  • DNA-Binding Proteins / genetics
  • Dietary Fats / adverse effects*
  • Dietary Fats / blood
  • Disease Models, Animal
  • Disease Progression
  • Fatty Liver / etiology*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Gene Expression Regulation
  • Heat-Shock Proteins / genetics
  • Heme Oxygenase (Decyclizing) / genetics
  • Interleukin-6 / genetics
  • Lipid Peroxidation
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Oxidative Stress
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Regulatory Factor X Transcription Factors
  • Time Factors
  • Transcription Factor CHOP / genetics
  • Transcription Factors / genetics
  • Triglycerides / blood
  • Weight Gain
  • X-Box Binding Protein 1
  • fas Receptor / genetics


  • DNA-Binding Proteins
  • Ddit3 protein, rat
  • Dietary Fats
  • Heat-Shock Proteins
  • Hspa5 protein, rat
  • Interleukin-6
  • RNA, Messenger
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • Triglycerides
  • X-Box Binding Protein 1
  • Xbp1 protein, rat
  • fas Receptor
  • Transcription Factor CHOP
  • Cholesterol
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Aspartate Aminotransferases
  • Alanine Transaminase