Troglitazone reduces the expression of PPAR gamma while stimulating that of PPAR alpha in mononuclear cells in obese subjects

We have recently demonstrated that troglitazone exerts an anti-inflammatory effect in the insulin resistant obese in vivo in parallel with its insulin -sensitizing effect. Because these effects are thought to be mediated throu gh peroxisome proliferator-activated receptors ct and gamma (PPAR alpha and PPAR gamma), we have now examined the possibility that troglitazone may mo dulate the expression of PPAR alpha and PPAR gamma. Seven obese hyperinsuli nemic subjects were administered 400 mg troglitazone daily for 4 weeks. Fas ting blood samples were obtained before and during troglitazone therapy at 1, 2, and 4 weeks. Fasting insulin concentrations fell at week I and persis ted at lower levels till 4 weeks. PPAR gamma expression fell significantly at week I and fell further : at weeks 2 and 4. In contrast, PPAR alpha expr ession increased significantly at week 2 and further at week 4. 9- and 13-h ydroxyoctadecanoic acid, products of Linoleic acid peroxidation and agonist s of PPAR gamma, decreased during troglitazone therapy. We conclude that tr oglitazone, an agonist for both PPAR alpha and PPAR gamma, has significant but dramatically opposite effects on PPAR alpha and PPAR gamma. These effec ts may be relevant to its insulin sensitizing and anti-inflammatory effects .