title: Development of alcoholic fatty liver and fibrosis in rhesus monkeys fed a low n-3 fatty acid diet.
abstract: BACKGROUND
  The amount and type of dietary fat seem to be important factors that modulate the development of alcohol-induced liver steatosis and fibrosis. Various alcohol-feeding studies in animals have been used to model some of the symptoms that occur in liver disease in humans.
  
  
  METHODS
  Rhesus monkeys (Macaca mulatta) were maintained on a diet that had a very low concentration of alpha-linolenic acid and were given free access to an artificially sweetened 7% ethanol solution. Control and ethanol-consuming animals were maintained on a diet in which the linoleate content was adequate (1.4% of energy); however, alpha-linoleate represented only 0.08% of energy. Liver specimens were obtained, and the fatty acid composition of the liver phospholipids, cholesterol esters, and triglycerides of the two groups were compared at 5 years and histopathology of tissue samples were compared at 3 and 5 years.
  
  
  RESULTS
  The mean consumption of ethanol for this group over a 5-year period was 2.4 g.kg.day. As a consequence of the ethanol-dietary treatment, there were significantly lower concentrations of several polyunsaturated fatty acids in the liver phospholipids of the alcohol-treated group, including arachidonic acid and most of the n-3 fatty acids and particularly docosahexaenoic acid, when compared with dietary controls. Liver specimens from animals in the ethanol group at 5 years showed a marked degree of steatosis, both focal and diffuse cellular necrosis, and an increase in the development of fibrosis compared with specimens obtained at 3 years and with those from dietary controls, in which there was no evidence of fibrotic lesions.
  
  
  CONCLUSIONS
  These findings suggest that the advancement of ethanol-induced liver disease in rhesus monkeys may be modulated by the amount and type of dietary essential fatty acids and that a marginal intake of n-3 fatty acids may be a permissive factor in the development of liver disease in primates.
authors.affiliation: Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Rockville, Maryland 20852, USA. bpawl@mail.nih.gov
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pawlosky
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
mesh_terms: D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use; D000431:Ethanol / Q000633:toxicity*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D005235:Fatty Liver, Alcoholic / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008253:Macaca mulatta; D008297:Male
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D000431:Ethanol