Total Inhibition of Hepatic β-Lipoprotein Production in the Rat by Orotic Acid

Lipoproteins of rat plasma have been characterized by lipid analysis, preparative ultracentrifugation, electrophoresis on paper, and immunoelectrophoresis with specific antisera to α-lipoprotein, β-lipoprotein, and whole rat plasma. Similar techniques were used to characterize the lipoproteins released by livers perfused in situ with a suspension of erythrocytes in a medium initially free of rat plasma proteins. Normal rat livers released α-lipoprotein, β-lipoprotein, albumin, and other plasma proteins during the perfusion. When rats were fed orotic acid as 1% of their diet, the plasma β-lipoprotein concentration fell within 7 days to less than 1% of normal. It rebounded to normal within 48 hours following withdrawal of orotic acid or supplementation of the diet with 0.17% of adenine. When perfused in situ, livers from orotic acid-fed rats released α-lipoprotein, albumin, and other plasma proteins but no detectable β-lipoprotein. They released smaller amounts of cholesterol and phospholipid than normal livers and no triglyceride, although they contained 10 times normal amounts of triglycerides. The fatty liver produced in rats by orotic acid appears to result from an inhibition of synthesis or release of hepatic β-lipoprotein, supporting the concept that β-lipoprotein has a specific role in the normal transport of triglyceride out of the liver.