The pleiotropic functions of peroxisome proliferator-activated receptor gamma

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for synthetic compounds that induce peroxisome proliferation. PPAR gamma is the best characterized of the PPARs. The heterodimer of PPAR gamma with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization. The RXR/PPAR gamma heterodimer furthermore has been reported to have important immunomodulatory activities and to affect cell proliferation/differentiation pathways in various malignancies. PPAR gamma is activated by a number of naturally occurring fatty acid derivatives and by several synthetic compounds, including the thiazolidinediones and L-tyrosine-based insulin sensitizers. This review gives an overview of the pleiotropic functions of PPAR gamma and discusses the wide-ranging medical implications that modulation of PPAR gamma activity might have for various diseases, ranging from obesity and type 2 diabetes to cancer and inflammation.