Ginsenoside 20(S)-protopanaxatriol (PPT) activates peroxisome proliferator-activated receptor gamma (PPAR gamma) in 3T3-L1 adipocytes

Peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear receptor of ligand-activated transcription factors, regulates the expression of key genes involved in lipid and glucose metabolism or adipocyte differentiation. Ligands for this receptor have emerged as potent insulin sensitizers used in the treatment of Type2 diabetes. Ginseng saponins or ginsenosides are reported to provide anti-diabetic activity as well as to modulate glucose metabolism, although the mechanism remains unclear. In this study, we examined the effect of ginsenosides on activation of PPAR gamma and adipogenes in 3T3-L1. Using a GAL-4/PPAR gamma transactivation assay, 20(S)protopanaxatriol (PPT), one of the ginsenoside metabolites, was found to increase PPAR gamma-transactivation activity dose-dependently with similar activity as troglitazone, a well-known PPAR gamma agonist. PPT enhanced adipogenesis by increasing the expression of PPAR gamma target genes such as aP2, LPL and PEPCK. Furthermore, PPT significantly increased expression of glucose transporter 4 (GLUT4). These results indicate that PPT can be developed as a PPAR gamma agonist for the improvement of insulin resistance associated with diabetes.