Synthesis and secretion of apo B containing lipoproteins by primary cultures of hepatocytes isolated from rats fed atherogenic diet

The effect of experimentally induced atherosclerosis on the synthesis and secretion of lipoproteins in the density range of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) have been studied using primary cultures of rat hepatocytes. Rats fed atherogenic diet showed higher levels of lipids associated with serum VLDL and LDL fraction, aorta and liver when compared with animals fed normal diet. Incorporation of [ 3H]leucine into apo B associated with the cell layer and secreted by hepatocytes from rats fed atherogenic diet was significantly more when compared with normal hepatocytes. [ 14C]Acetate incorporation studies showed that the synthesis of cholesterol was lower in hepatocytes from atherogenic diet fed rats, but more of the newly synthesised cholesterol was found in the secreted VLDL; secretion of lipids, particularly triglycerides, unesterified cholesterol and cholesterol in the lipoproteins in the density range of VLDL and LDL was significantly more in these hepatocytes. The relative distribution of [ 3H]-radioactivity in the LDL density range was 57% in hepatocytes from atherogenic diet fed animals as compared with 28% in controls, suggesting a relatively higher production of lipoproteins in the LDL density range than VLDL by these cells. These results indicate that the hypercholesterolemia in atherogenic diet fed animals may among other factors be caused by increased synthesis of apo B by liver cells and resultant increase in the secretion of apo B containing lipoproteins.