Peroxisome proliferator-activated receptor gamma (PPAR gamma) activation and its consequences in humans

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member o f the superfamily of nuclear receptors. It binds and is activated by natura l polyunsaturated fatty acids, eicosanoids, synthetic thiazolidinediones an d related analogues. Biological effects exerted by PPAR gamma ligands are m ostly concerned with differentiation processes, sensitization to insulin an d atherogenesis, and are paradigmatically ascribed to PPAR gamma transactiv ation of PPAR gamma -responsive genes. The PPAR gamma paradigm and its cons equences in humans are analyzed here in terms of the tissue specificity of PPAR gamma, loss and gain of function mutants of PPAR gamma, PPAR gamma -re sponsive genes and clinical effects of PPAR gamma ligands. Differentiation, as well as some of the atherogenic effects induced by PPAR gamma ligands, does conform to the PPAR gamma paradigm. However, sensitization to insulin as well as some of the antiatherogenic effects of PPAR gamma ligands is not accounted for by PPAR gamma activation, thus calling for an alternative ta rget for insulin sensitizers. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.