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Development of Alcoholic Fatty Liver and Fibrosis in Rhesus Monkeys Fed a Low n‐3 Fatty Acid Diet
Author(s) -
Pawlosky Robert J.,
Salem Norman
Publication year - 2004
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000141810.22855.4e
Subject(s) - steatosis , docosahexaenoic acid , fatty liver , polyunsaturated fatty acid , ethanol , steatohepatitis , arachidonic acid , medicine , alpha linolenic acid , fibrosis , alcohol , fatty acid , cholesterol , endocrinology , histopathology , liquid diet , biology , chemistry , biochemistry , pathology , disease , enzyme
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 α‐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, α‐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 −1 · day −1 . 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. Conclusion: 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.