EFFECTS OF TREATMENT OF HYPERTRIGLYCERIDEMIA WITH GEMFIBROZIL ON SERUM-LIPOPROTEINS AND THE TRANSFER OF CHOLESTERYL ESTER FROM HIGH-DENSITY-LIPOPROTEINS TO LOW-DENSITY LIPOPROTEINS

Lipoprotein composition and cholesterol esterification, before and after treatment with gemfibrozil, have been examined in the fasting and postprandial state in nine patients with primary hypertriglyceridaemia who participated in a double-blind, placebo controlled study. After 8 weeks of treatment fasting serum triglycerides were reduced significantly from 6.05 mmol/l (range 2.48-10.99 mmol/l) to 1.76 mmol/l (range 1.16-11.90 mmol/l) (P < 0.001). This was mainly due to a decrease in the triglyceride content of the Sf 12-20, 60-400 and Sf > 400 lipoprotein fractions (P < 0.05). The Sf 0-12 fraction showed an increase in cholesteryl ester, free cholesterol, phospholipids and protein. Consistent with these findings there was a net increase in the mass concentration of the Sf 0-12 fraction (P < 0.05) and a decrease in that of small very low density lipoproteins (Sf 20-60) (P < 0.05). In the 8 patients in whom it was measured there was a 40% reduction in the rate at which cholesteryl esters derived from radiolabelled-free cholesterol appeared in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) measured in an in vitro system (P < 0.02), but serum lecithin:cholesterol acyl transferase (LCAT) activity was unchanged. At the end of each treatment phase (placebo or gemfibrozil) patients were given a mixed meal containing 100 g of fat. Treatment with gemfibrozil resulted in a reduction in serum triglyceride concentrations at all time points for at least 5 h after the meal (P < 0.001). Treatment with gemfibrozil also resulted in a significant reduction in the postprandial triglyceride content of Sf 0-12 and Sf 60-400 lipoprotein subfractions and cholesteryl ester content of the Sf 20-60 subfraction. The transfer of newly esterified cholesterol from high-density lipoproteins (HDL) to VLDL and LDL measured in vitro was decreased by gemfibrozil throughout the postprandial period (P < 0.05). Thus both in the fasting and postprandial states a decrease in the circulating serum triglyceride levels by gemfibrozil may decrease the rate of transfer of newly esterified cholesterol into VLDL and LDL.