PPAR activation as a regulator of lipid metabolism, nitric oxide production and lipid peroxidation in the placenta from type 2 diabetic patients

Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, anti-inflammatory processes and placental development. Maternal diabetes induces a pro-inflammatory environment and alters placental development. We investigated whether PPARs regulate lipid metabolism and nitric oxide (NO) production in placental explants from healthy and type 2 diabetic (DM2) patients. We found decreased PPAR alpha and PPAR gamma concentrations, no changes in PPAR delta concentrations, and increased lipids, lipoperoxides and NO production in placentas from DM2 patients. PPAR alpha agonists reduced placental concentrations of triglycerides and both PPAR alpha and PPAR delta agonists reduced concentrations of phospholipids, cholesteryl esters and cholesterol. PPAR gamma agonists increased lipid concentrations in placentas from DM2 patients and more markedly in placentas from healthy patients. Endogenous ligands for the three PPAR isotypes reduced NO production and lipoperoxidation in placentas from DM2 patients. We conclude that PPARs play a role in placental NO and lipid homeostasis and can regulate NO production, lipid concentrations and lipoperoxidation in placentas from DM2 patients. (c) 2013 Elsevier Ireland Ltd. All rights reserved.