The effects of diet cholesterol on the synthesis of rat serum apolipoproteins

Abstract

The major objectives of this study were to determine the effects of diet cholesterol on serum apoprotein synthesis and to test the hypothesis that the synthesis of serum high density apoprotein and cholesterogenesis may be interrelated. The relative rates of synthesis of serum apoproteins were determined by assay of apoprotein radioactivity at 30 minute intervals after intraperitoneal injection of [4, 5 - ³H] leucine. The rate of incorporation of labeled leucine into apoproteins of high density lipoproteins (HDL) was significantly lower in male rats ingesting 1% cholesterol for 14 days than in those animals receiving no cholesterol. Reduction of apo HDL synthesis was accompanied by an increase in the synthesis of very low density apoprotein (VLDL). Changes in apoprotein synthesis were specific for cholesterol and independent of the nature of diet fat. Replacement of diet cholesterol by an equivalent level of squalene produced results carparable to those observed in animals fed no cholesterol. Turnover studies revealed that diet cholesterol slightly increased the rate of degradation of VLDL apoprotein but had no effect on the rate of catabolism of HDL apoprotein. Concentrations and specific radioactivities of serum high density apoproteins in groups of animals fed different amounts of cholesterol for 14 days were found to be inversely proportional to total cholesterol in hepatic tissue. Sapid changes in both apoprotein and cholesterol synthesis occurred during the first 3 1/2 days after 0.5% cholesterol was included in the diet. Reduction of apo HDL and cholesterol synthesis, determined by simultaneously injecting [4,5-³H] leucine and [1- ¹⁴C] acetate, was evident as early as 1 1/2 days after animals had access to cholesterol diets..