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 stud ied using primary cultures of rat hepatocytes. Rats fed atherogenic di et showed higher levels of lipids associated with serum VLDL and LDL f raction, aorta and liver when compared with animals fed normal diet. I ncorporation of [H-3]leucine into apo B associated with the cell layer and secreted by hepatocytes from rats fed atherogenic diet was signif icantly more when compared with normal hepatocytes. [C-14]Acetate inco rporation studies showed that the synthesis of cholesterol was lower i n hepatocytes from atherogenic diet fed rats, but more of the newly sy nthesised cholesterol was found in the secreted VLDL; secretion of lip ids, particularly triglycerides, unesterified cholesterol and choleste rol in the lipoproteins in the density range of VLDL and LDL was signi ficantly more in these hepatocytes. The relative distribution of [H-3] -radioactivity in the LDL density range was 57% in hepatocytes from at herogenic diet fed animals as compared with 28% in controls, suggestin g a relatively higher production of lipoproteins in the LDL density ra nge than VLDL by these cells. These results indicate that the hypercho lesterolemia in atherogenic diet fed animals may among other factors b e caused by increased synthesis of apo B by liver cells and resultant increase in the secretion of apo B containing lipoproteins.