Reciprocal responses to clofibrate in ketogenesis and triglyceride and cholesterol secretion in isolated rat liver

Abstract

The effect of clofibrate on the production of ketone bodies and the secretion of lipids was examined in the isolated rat liver. Feeding of clofibrate (0.3% in the diet) for a week caused the liver enlargement. The drug increased ketone body production and conversely decreased the secretion of triglyceride and cholesterol in the perfused liver, in particular when oleate was provided to the perfusion medium. Fractionation of the liver perfusate at the density of 1.006 g/ml showed that changes in the rate of lipid secretion were largely due to the modification of the rate of very low density lipoprotein secretion. These observations indicated that the enhancement of fatty acid oxidation by clofibrate resulted in the concomitant decrease in the flux of free fatty acid into triglyceride synthesis and subsequent formation and secretion of triglyceride-rich lipoproteins in the liver. Measurement of activities of enzymes involved in hepatic cholesterogenesis proved that the alteration of the rate of hepatic cholesterogenesis might not be a factor responsible for the hypocholesterolemic action of clofibrate.