Effect of bezafibrate on lipoprotein secretion by cultured human hepatocytes

The secretion of newly synthesized very low density lipoprotein and low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) in cultured human hepatocytes in the presence or absence of bezafibrate added to the culture medium has been evaluated. The content of triacylglycerol, apolipoprotein B, 3H-labeled proteins and 14C-labeled lipids accumulated in a culture medium increased linearly for periods up to 18 h. During incubation, cellular triacylglycerol content was unchanged. This hypolipidemic agent, at a concentration of 10 microM, inhibited secretion of the several VLDL + LDL [3H]apolipoproteins and the VLDL + LDL [14C]lipids, suggesting it can affect the processes of biosynthesis and secretion. The secretion of total [3H]apolipoproteins in the HDL fraction and [3H]protein (d greater than 1.21 g/ml) was unchanged after an exposure to bezafibrate (10 microM). Incubation in the presence of 10 microM bezafibrate resulted also in decreases in both total VLDL neutral lipids and apolipoprotein B secreted into the medium. These results indicate that bezafibrate might exert its plasma lipid-lowering effect by suppressing the VLDL production in liver and reducing the secretion of VLDL into the circulation.