Role of PPAR-gamma in Inflammation. Prospects for Therapeutic Intervention by Food Components

Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. Acting as sensors of hormones, vitamins, endogenous metabolites and xenobiotic compounds, the nuclear receptors control the expression of a very large number of genes. PPARgamma has been known for some time to regulate adipocyte differentiation, fatty acid storage and glucose metabolism, and is a target of anti-diabetic drugs. More recently, PPARgamma has been recognized as playing a fundamentally important role in the immune response through its ability to inhibit the expression of inflammatory cytokines and to direct the differentiation of immune cells towards anti-inflammatory phenotypes. A feature of PPARgamma is the structural diversity of its ligands, which encompass endogenous metabolites, dietary compounds and synthetic drugs. The high and increasing incidence of inflammatory and allergic disease, coupled with encouraging results from recent clinical trials, suggest that natural PPARgamma agonists found in foods may be beneficial to human health by acting as anti-inflammatory molecules. PPARgamma is therefore not only a target of the pharmaceutical industry, but also of great potential interest to the food industry, since it is activated by several natural dietary constituents. The prospects for dietary intervention in inflammatory disease have improved somewhat over the last few years, and are reviewed here.