The pleiotropic functions of peroxisome proliferator-activated receptor γ

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for synthetic compounds that induce peroxisome proliferation. PPARγ is the best characterized of the PPARs. The heterodimer of PPARγ with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization. The RXR/PPARγ heterodimer furthermore has been reported to have important immunomodulatory activities and to affect cell proliferation/differentiation pathways in various malignancies. PPARγ 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 PPARγ and discusses the wide-ranging medical implications that modulation of PPARγ activity might have for various diseases, ranging from obesity and type 2 diabetes to cancer and inflammation.