The Induction of Hepatic Cholesterol Synthesis in the Rat by Lecithin Mesophase Infusions

A 4-hour intravenous infusion of egg lecithin in the rat produced a significant increase in hepatic cholesterol synthesis from acetate in both liver slices and homogenates. Direct in vitro additions of lecithin to the homogenates produced no change in the conversion to acetate to cholesterol. Mevalonate conversion to cholesterol in both homogenates and slices was unchanged by lecithin infusions. An increase of similar magnitude in the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase was seen after the lecithin infusion. This increase in enzyme activity was associated with a significantly lower microsomal cholesterol content. The increase in cholesterol synthesis was prevented when the infused lecithin was made to molar ratios of cholesterol to lecithin greater than 0.5:1. Cholesterol-lecithin infusions with molar ratios of 1:1 appeared to inhibit conversion of acetate to cholesterol. The cholesterol content of the microsomes following these infusions was greater than control. Pretreatment of the animals with cycloheximide abolished the activation of cholesterol synthesis by lecithin, but actinomycin D had no effect.