3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE INHIBITOR IMPAIRS CELL-DIFFERENTIATION IN CULTURED ADIPOGENIC CELLS (3T3-L1)

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibito r, inhibits the synthesis of mevalonic acid. We examined the effect of lovastatin on the differentiation of the fibroblast/adipocyte cell li ne (3T3-L1). Lovastatin inhibits the differentiation of 3T3-L1 cells i n a dose-dependent fashion. The inhibitory effect of lovastatin was pa rtially reversed by adding exogenous mevalonic acid to the 3T3-L1 cell s. Exogenous cholesterol (15 mu g/ml) did not prevent lovastatin inhib ition of adipocyte conversion. The isoprenoids, farnesol and geraniol, partially prevented lovastatin inhibition of adipocyte conversion but squalene did not prevent lovastatin inhibition of adipocyte conversio n. We conclude that the inhibitory effect of lovastatin was partially due to the blockade of the pathway leading to synthesis of isoprenoids , which are downstream products of mevalonic acid.