Receptor-independent Actions of PPAR Thiazolidinedione Agonists: Is Mitochondrial Function the Key?

Biochem Pharmacol. 2005 Jul 15;70(2):177-88. doi: 10.1016/j.bcp.2005.03.033.

Abstract

Agonists of the peroxisome proliferator activated receptor gamma (PPAR(gamma)) are currently used for treatment of type 2 diabetes due to their insulin sensitizing and glucose metabolism stabilizing effects. More recently some of these same agonists were shown to exert anti-inflammatory and anti-proliferative effects as well. Although PPAR(gamma) agonists can operate via receptor-mediated events occurring at the genomic level, thereby causing long lasting changes in gene expression patterns, recent studies demonstrate non-genomic as well as genomic actions, and receptor-dependent as well as receptor-independent effects of the thiazolidinedione (TZD) class of PPAR(gamma) agonists. In this review we will summarize data describing some of these novel, receptor independent actions of TZDs, review evidence that TZDs directly influence mitochondrial function, and attempt to reconcile how changes in mitochondrial function could contribute to other receptor-independent actions of these drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / physiology*
  • PPAR gamma / agonists*
  • PPAR gamma / physiology
  • Thiazolidinediones / pharmacology*

Substances

  • PPAR gamma
  • Thiazolidinediones