Studies on fatty liver induction by 4-aminopyrazolopyrimidine

The effects of the adenine analogue, 4-aminopyrazolopyrimidine, on lipid metabolism in mouse liver have been studied in an attempt to ascertain the mechanism by which this drug causes fatty livers. Injection of I mg of APP caused an increase in the total liver lipid of 3- to 4-fold in 24 hr, which was almost entirely accounted for as neutral lipid. There was a small increase in the cholesterol content of treated livers, but no change in the amount of phospholipid. Treatment with APP inhibited the incorporation of acetate-C14 into lipids of liver slices in vitro, but had little effect on the oxidation of acetate-C14 and palmitate-C14 in vitro. The plasma lipid concentration was decreased by APP treatment, and this was caused by a drop in triglycerides and cholesterol, whereas phospholipids and FFA did not change. Palmitate-C14 was taken up less well by livers of mice treated with APP than by livers of control mice. Although APP caused a profound inhibition of incorporation of orotic acid-C14 into RNA, the incorporation of glycine-C14 Into liver and plasma proteins was not diminished. The hyperlipemia normally elicited by Triton WR-1339 was inhibited by APP, which strongly suggests that this compound inhibits the secretion of triglycerides from the liver.