Troglitazone reduces the expression of PPARγ while stimulating that of PPARα in mononuclear cells in obese subjects

Ahmad Aljada, Husam Ghanim, Jay Friedman, Rajesh Garg, Priya Mohanty, Paresh Dandona

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 a and γ (PPARα and PPARγ), we have now examined the possibility that troglitazone may modulate the expression of PPARα and PPARγ. 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. PPARγ expression fell significantly at week 1 and fell further at weeks 2 and 4. In contrast, PPARα expression increased significantly at week 2 and further at week 4.9- and 13-hydroxyoctadecanoic acid, products of linoleic acid peroxidation and agonists of PPARγ, decreased during troglitazone therapy. We conclude that troglitazone, an agonist for both PPARα and PPARγ has significant but dramatically opposite effects on PPARα and PPARγ These effects may be relevant to its insulin sensitizing and anti-inflammatory effects.

Original languageEnglish (US)
Pages (from-to)3130-3133
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number7
DOIs
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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