PPARα agonists regulate lipid metabolism and nitric oxide production and prevent placental overgrowth in term placentas from diabetic rats

Maternal diabetes impairs fetoplacental metabolism and growth. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a nuclear receptor capable of regulating lipid metabolism and inflammatory pathways. In this study, we analyzed whether placental and fetal PPAR alpha activation regulates lipid metabolism and nitric oxide (NO) production in term placentas from diabetic rats. Diabetes was induced by neonatal streptozotocin administration. On day 21 of pregnancy, placentas from control and diabetic rats were cultured in the presence of PPAR alpha agonists (clofibrate and leukotriene B-4 (LTB4)) for further evaluation of levels, synthesis, and peroxidation of lipids as well as NO production. Besides, on days 19, 20, and 21 of gestation, fetuses were injected with LTB4, and the placentas were explanted on day 21 of gestation for evaluation of placental weight and concentrations of placental lipids, lipoperoxides, and NO metabolites. We found that placentas from diabetic rats showed reduced PPAR alpha concentrations. They presented no lipid overaccumulation but reduced lipid synthesis, parameters negatively regulated by PPAR alpha activators. Lipid peroxidation and NO production, increased in placentas from diabetic rats, were negatively regulated by PPAR alpha activators. Fetal PPAR alpha activation in diabetic rats does not change placental lipid concentrations but reduced placental weight and NO production. In conclusion, PPAR alpha activators regulate lipid metabolism and NO production in term placentas from diabetic rats, an activation that regulates placental growth and can partly be exerted by the developing fetus.