PPARγ Regulation in Hypertension and Metabolic Syndrome.

Dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) activity leads to significant alterations in cardiovascular and metabolic regulation. This is most keenly observed by the metabolic syndrome-like phenotypes exhibited by patients carrying mutations in PPARγ. We will summarize recent findings regarding mechanisms of PPARγ regulation in the cardiovascular and nervous systems focusing largely on PPARγ in the smooth muscle, endothelium, and brain. Canonically, PPARγ exerts its effects by regulating the expression of target genes in these cells, and we will discuss mechanisms by which PPARγ targets in the vasculature regulate cardiovascular function. We will also discuss emerging evidence that PPARγ in the brain is a mediator of appetite and obesity. Finally, we will briefly review how novel PPARγ activators control posttranslational modifications of PPARγ and their prospects to offer new therapeutic options for treatment of metabolic diseases without the adverse side effects of thiazolidinediones which strongly activate transcriptional activity of PPARγ.