Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells

Statins increase peroxisome proliferator-activated receptor α (PPAR α ) mRNA expression, but the mechanism of this increased PPAR α production remains elusive. To examine the regulation of PPAR α production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPAR α promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPAR α promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR α promoter. This enhancement may be mediated by statin-induced HNF-4 α . (2) PPAR α mRNA expression was increased by statin treatment. (3) The PPAR α levels in nuclear fractions were increased by statin treatment. (4) Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR α /RXR α expression vectors. In summary, these data demonstrate that PPAR α production and activation are upregulated through the PPAR α promoter activity by statin treatment.