The effect of bezofibrate and clofibrate on cholesterol accumulation, esterification and removal in cultured 3T3 fibroblasts.

3T3 mouse fibroblasts were used to determine the effect of bezafibrate and clofibrate on the cellular metabolism of cholesterol. In cells incubated in normal medium these agents decreased the incorporation of 3H-labelled oleic acid relative to 14C-labelled linoleic acid into the cholesterol ester fraction. When the 3T3 fibroblasts were incubated with cationised low density lipoprotein (LDL) the amount of esterified cholesterol which accumulated in the cells was greatly increased. This accumulation of cholesterol ester was reduced by bezafibrate and clofibrate. These agents decreased the incorporation of both 3H-labelled oleic acid and 14C-labelled linoleic acid into the cholesterol ester fraction of the cells, with a preferential effect on oleic acid as indicated by a reduction in the 3H/14C ratio. When cells which had been preincubated with cationised LDL were reincubated in normal medium, the removal of esterified cholesterol from the cells was increased by both bezafibrate and clofibrate. The mechanism of the effects of these agents on the metabolism of cellular cholesterol is discussed.