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Troglitazone Reduces the Expression of PPAR While Stimulating That of PPAR in Mononuclear Cells in Obese Subjects¹

Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209

Address all correspondence and requests for reprints to: Paresh Dandona, M.D., Ph.D., Diabetes-Endocrinology Center of WNY, 3 Gates Circle, Buffalo, New York 14209. E-mail: pdandona{at}kaleidahealth.org

Abstract

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 through peroxisome proliferator-activated receptors and (PPAR and PPAR), we have now examined the possibility that troglitazone may modulate the expression of PPAR and PPAR. Seven obese hyperinsulinemic subjects were administered 400 mg troglitazone daily for 4 weeks. Fasting blood samples were obtained before and during troglitazone therapy at 1, 2, and 4 weeks. Fasting insulin concentrations fell at week 1 and persisted at lower levels till 4 weeks. PPAR expression fell significantly at week 1 and fell further at weeks 2 and 4. In contrast, PPAR expression increased significantly at week 2 and further at week 4. 9- and 13-hydroxyoctadecanoic acid, products of linoleic acid peroxidation and agonists of PPAR, decreased during troglitazone therapy. We conclude that troglitazone, an agonist for both PPAR and PPAR, has significant but dramatically opposite effects on PPAR and PPAR. These effects may be relevant to its insulin sensitizing and anti-inflammatory effects.

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