Effect of clofibrate on lipoprotein metabolism in hyperlipidemic rats

The effects of clofibrate administration were studied in rats made hyperlipidemic by the feeding of diets high in sucrose. Within 12 hr of administration of clofibrate, there was a marked decrease in the concentration of serum high density lipoproteins but no change in the concentrations of the low and very low density lipoproteins. Between 2-4 days of treatment, the concentration of the very low density lipoproteins decreased whereas that of the low density lipoproteins was unchanged. In addition, the composition of the very low density lipoproteins was altered by clofibrate administration with a decrease in triglyceride and an increase in phospholipid content. The synthesis of high density lipoproteins, as measured by the incorporation of labeled amino acids, decreased within 12 hr of treatment. The synthesis of the very low density lipoproteins was increased during the first 2 days and then decreased slightly. The synthesis of low density lipoproteins did not change. The rate of removal of very low density lipoproteins was measured at various times from 0.5 to 8 days of treatment and was found to be elevated. It was concluded that in the hyperlipidemic sucrose-fed rat, administration of clofibrate results in a reduced level of very low density lipoproteins which may be due in part to enhancement of the rate of removal of this fraction.