Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the superfamily of nuclear receptors. It binds and is activated by natural polyunsaturated fatty acids, eicosanoids, synthetic thiazolidinediones and related analogues. Biological effects exerted by PPARγ ligands are mostly concerned with differentiation processes, sensitization to insulin and atherogenesis, and are paradigmatically ascribed to PPARγ transactivation of PPARγ-responsive genes. The PPARγ paradigm and its consequences in humans are analyzed here in terms of the tissue specificity of PPARγ, loss and gain of function mutants of PPARγ, PPARγ-responsive genes and clinical effects of PPARγ ligands. Differentiation, as well as some of the atherogenic effects induced by PPARγ ligands, does conform to the PPARγ paradigm. However, sensitization to insulin as well as some of the antiatherogenic effects of PPARγ ligands is not accounted for by PPARγ activation, thus calling for an alternative target for insulin sensitizers.
Original language | English |
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Pages (from-to) | 9-19 |
Number of pages | 11 |
Journal | Toxicology Letters |
Volume | 120 |
Issue number | 1-3 |
DOIs | |
State | Published - 31 Mar 2001 |
Keywords
- Atherosclerosis
- Differentiation
- Insulin resistance
- PPARγ
- Thiazolidinediones