Rabbit Anti-Human PPARG (Phospho-Ser112) polyclonal antibody

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that represent an effective class of insulin-sensitizing agents; however, clinical use is associated with weight gain and peripheral edema. To elucidate the role of PPAR gamma expression in endothelial cells (ECs) in these side effects, EC-targeted PPAR gamma knockout (Pparg(Delta EC)) mice were placed on a high-fat diet to promote PPAR gamma agonist-induced plasma volume expansion, and then treated with the TZD rosiglitazone. Compared with Pparg-floxed wild-type control (Pparg(f/f)) mice, Pparg(Delta EC) treated with rosiglitazone are resistant to an increase in extracellular fluid, water content in epididymal and inguinal white adipose tissue, and plasma volume expansion. Interestingly, histologic assessment confirmed significant rosiglitazone-mediated capillary dilation within white adipose tissue of Pparg(f/f )mice, but not Pparg(Delta EC) mice. Analysis of ECs isolated from untreated mice in both strains suggested the involvement of changes in endothelial junction formation. Specifically, compared with cells from Pparg(f/f) mice, Pparg(Delta EC) cells had a 15-fold increase in focal adhesion kinase, critically important in EC focal adhesions, and >3-fold significant increase in vascular endothelial cadherin, the main component of focal adhesions. Together, these results indicate that rosiglitazone has direct effects on the endothelium via PPAR gamma activation and point toward a critical role for PPAR gamma in ECs during rosiglitazone-mediated plasma volume expansion.