Secretion of very low density lipoproteins by cultured rabbit hepatocytes with hypercholesteremia, induced by purified cholesterol and containing autooxidation products

To evaluate the impact of oxidized derivatives of cholesterol on the development of hypercholesterolemia in rabbits, the secretion of very low density lipoprotein (VLDL) apoproteins and lipids was studied in cultures of hepatocytes obtained from: i) control rabbits, ii) rabbits fed on purified cholesterol (PCH), and, iii) rabbits fed on old commercial cholesterol (OCH) containing 5% of oxidized cholesterol derivatives. The rabbits fed on OCH for 6 weeks revealed a 5-fold increase in the serum cholesterol level compared with that in PCH-fed rabbits. The secretion of VLDL apoproteins and lipids by hepatocytes of two cholesterol-fed groups was similar, but was 2-3 times as high as that of cells from control rabbits. The cholesterol ester content in hepatocytes and the secretion of VLDL cholesterol esters by hepatocytes from OCH-fed rabbits was dramatically increased in comparison with hepatocytes from control and PCH-fed rabbits. These effects appear to be caused by the activation of cholesterol esterification by oxidized cholesterol derivatives. The rapid development of hypercholesterolemia in OCH-fed rabbits is at least partly associated with the stimulation of hepatic VLDL production.