PPARγ ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages

Recently it has been reported that macrophages express a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma). Using a ligand of PPARgamma, troglitazone or pioglitazone, we have shown that the expression of two genes involved in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were increased by activation of PPARgamma through a PPAR response element (PPRE) in THP-1 macrophages. In addition, treatment with troglitazone significantly increased the activity of HMG-CoA reductase and the amount of intracellular cholesterol. Thus, we conclude that PPARgamma and its agonists increase the cholesterol content of macrophages by the increased expression of genes involved in cholesterol biosynthesis. These findings suggest that PPARgamma may play a role in cholesterol metabolism in macrophages. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.