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Factors Influencing the Induction of Fatty Liver by Orotic Acid^1,2,

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Female Wistar strain rats were fed purified diets containing orotic acid, and the influence of diet on orotic acid induced fatty liver was studied. Starved animals receiving daily 100 to 200 mg orotic acid or other pyrimidines or purines for 1 to 3 days did not develop fatty livers. Animals fed ad libitum the purified diet and tube-fed separately 100 mg orotic acid daily for 3 days did not develop fatty livers. Animals force-fed for 3 days an adequate amount of purified diet containing 1% orotic acid but not those force-fed one-half amount of diet containing 2% orotic acid developed fatty livers. Animals force-fed for 3 days an orotic acid-containing diet in which casein was replaced by casein hydrolyzate or purified amino acids failed to develop fatty livers. Animals fed ad libitum for 7 days an orotic acid-containing diet, in which casein, lactalbumin or soybean (protein or its hydrolyzate) was used, developed marked fatty livers in all animals except those fed the casein hydrolyzate diet where only mild fatty livers developed. These results indicate the importance of the nature and quantity of the diet in the induction of fatty liver by orotic acid.

² Supported in part by research grants from the National Institute of Arthritis and Metabolic Diseases, U.S. Public Health Service (AM05908 and AM06344) and the Allegheny County Health Research and Services Foundation (E-24). Dr. Lombardi is a recipient of a U.S. Public Health Service Research Career Development Award (5-K3-14,823).

Manuscript received 14 June 1963.