Effect of lipoprotein-X on hepatic cholesterol synthesis

The effect of different lipoproteins (lipoprotein-X and lipoprotein-B; LP-X and LP-B) on hepatic cholesterol synthesis was studied in vivo in rats. Lipoproteins were continuously infused into rats for 16 hours so that 24 mg cholesterol/100 g body weight were applied. Serum cholesterol level was nearly doubled after the infusion period. Lipoprotein electrophoresis revealed the predominance of the infused lipoprotein in the serum. LP-B infusion caused a reduction of cholesterol synthesis (42% of control values) and reduced the increased cholesterol synthesis of bile fistula rats to values below normal. LP-X did not reduce hepatic cholesterol synthesis significantly nor did it normalize the enhanced synthesis following biliary diversion. However, hepatic free cholesterol concentration increased after LP-X infusion. The effect of LP-X on liver cholesterol synthesis is similar to that of lecithin: cholesterol dispersions. The failure of LP-X to exert a feedback inhibition on cholesterol synthesis may therefore contribute to the mechanism of hypercholesterolemia in obstructive jaundice.