ASSOCIATION BETWEEN HEPATIC TRIACYLGLYCEROL ACCUMULATION INDUCED BY ADMINISTERING OROTIC-ACID AND ENHANCED PHOSPHATIDATE PHOSPHOHYDROLASE ACTIVITY IN RATS

Orotic acid is known to cause fatty liver, bat it is unclear whether t his is caused partly by stimulation of the enzymes for triacylglycerol (TG) synthesis. To understand the change of hepatic TG metabolism in fatty liver induced by erotic acid, we determined the liver tissue TG level and phosphatidate phosphohydrolase (PAP) activity over time in r ats fed on a diet containing orotic acid (OA), ih dietary lipid conten t of 10% was achieved by using n-6 fatty acid-rich corn oil in experim ent I, and n-6 fatty acid-rich safflower ed (SO) and n-3 fatty acid-ri ch fish oil (FO) with the same polyunsaturated fatty acid/monounsatura ted fatty acid/saturated fatty acid (P/M/S) ratio in experiment 2, In experiment 1, an increase in the hepatic TG level due to OA intake was observed from day 5 onwards, the level rising approximately 6-fold by day 10. The activity of hepatic microsomal PAP, the rate-limiting enz yme in TG synthesis, increased markedly from day 5 onwards, concurrent with the liver diacylglycerol concentration. A strong correlation (r = 0.974) was observed between the hepatic TG level and microsome-bound PAP activity. In experiment 2, we investigated the effects of dietary fatty acid on CBA-induced fatty liver. Compared,vith the nd fatty aci d-rich vegetable oil diet, the relative increase in hepatic TG was sma ller with the n-3 fatty acid-rich FO diet, and hepatic PAP activity fe ll markedly to the level for an OA-free diet. In addition, the hepatic TG accumulation and serum TG concentration were lower in the FO group than in the SO group, Nevertheless, because the hepatic TG level was low, it seems that the inhibition of liver PAP activity by FO possibly had a strong influence on the accumulation of TG in the liver. In con clusion, enhanced TG synthesis mediated by changes in liver PAP activi ty was involved in the hepatic TG accumulation induced by OA administr ation, this change being markedly suppressed by dietary n-3 fatty acid s.