The metabolism of chylomicron remnants by isolated perfused rat liver

Abstract

When whole chylomicrons containing radiolabeled lipids were added to the perfusate of an isolated liver, virtually no cholesterol ester or triacylglycerol was removed during the first hour, while a small amount of free cholesterol disappeared. After 3 h, 40% of the cholesterol ester was removed by the liver. In contrast, when chylomicron remnants, prepared by incubation of chylomicrons with post heparin plasma and containing the same amount of cholesterol, were added to the perfusate, 76 ± 7% of the cholesterol ester was removed in the first hour. Moreover, free cholesterol and triacylcerol disappeared from the perfusate at the same rate as the cholesterol ester and during the early phase of the perfusion, the total perfusate cholesterol content declined by the same amount as the radioactive cholesterol content. These results suggest a specific removal of the intact lipoprotein particle. Of the cholesterol ester removed, 42% was hydrolyzed to free cholesterol after three hours. When whole chylomicrons, containing the same amount of cholesterol, were injected into rats in vivo, 71 ± 4% of the cholesterol ester was removed by the liver in three hours and 53% of this was hydrolyzed. Finally, the activity of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis, increased during liver perfusion with plasma-free, or chylomicron-containing perfusate while addition of chylomicron remnants to the perfusate significantly diminished the effect. It is concluded that the chylomicron remnant is the lipo-protein of alimentary origin which regulates hepatic cholesterol synthesis, and that its metabolism by isolated liver appears to reflect the hepatic component of chylomicron metabolism in vivo.