The Induction of Liver Cirrhosis in Rats by Purified Amino Acid Diets^1 2

Rats were fed lipotrope-deficient or control diets using purified amino acids as the source of dietary essential and nonessential amino acids. The amino acid mixtures were based on the composition of casein or on amino acid diets previously shown to result in normal growth in rats. Livers from deficient rats were fatty after 10 weeks and cirrhotic after 4 months to 1 year. Liver lipids reached a maximum of 69% of the dry weight. Triglyceride accounted for the bulk of the increase, but cholesterol was also significantly increased while phospholipid was unchanged. All 3 lipid fractions decreased in the serum of deficient rats. These findings are in agreement with the results of lipotrope deficiency in rats fed intact protein. DNA synthesis in parenchymal cells, measured in emulsion autoradiographs from rats given thymidine-³H, increased in fatty livers and then returned to normal as cirrhosis progressed. Chemical and morphologic findings indicated that fatty nutritional cirrhosis, characteristic of lipotrope deficiency, and identical to that induced with intact proteins, was induced with the l-amino acid diets. The severity of the lesions and the time of onset appeared to be more consistent than has been found with deficient diets containing intact proteins. l-Amino acid diets should be particularly useful in assessing the effect of fatty nutritional cirrhosis on the induction of liver damage by hepatic carcinogens and further eliminate the uncertainty of possible unknown contaminants inherent in intact proteins.