Bile Acids Induce the Expression of the Human Peroxisome Proliferator-Activated Receptor α Gene via Activation of the Farnesoid X Receptor

Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that controls lipid and glucose metabolism and exerts antiinflammatory activities. PPARα is also reported to influence bile acid formation and bile composition. Farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor that mediates the effects of bile acids on gene expression and plays a major role in bile acid and possibly also in lipid metabolism. Thus, both PPARα and FXR appear to act on common metabolic pathways. To determine the existence of a molecular cross-talk between these two nuclear receptors, the regulation of PPARα expression by bile acids was investigated. Incubation of human hepatoma HepG2 cells with the natural FXR ligand chenodeoxycholic acid (CDCA) as well as with the nonsteroidal FXR agonist GW4064 resulted in a significant induction of PPARα mRNA levels. In addition, hPPARα gene expression was up-regulated by taurocholic acid in human primary hepatocytes. Cotransfection of FXR/retinoid X receptor in...