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

MARTINEZ NORA; KURTZ MELISA; CAPOBIANCO EVANGELINA; HIGA ROMINA; WHITE VERÓNICA; JAWERBAUM ALICIA

JOURNAL OF MOLECULAR ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Año: 2011 vol. 47 p. 1 - 12

0952-5041

Maternal diabetes impairs feto-placental metabolism and growth. Peroxisome proliferator activated receptor a (PPARa) is a nuclear receptor capable of regulating lipid metabolism and inflammatory pathways. We here analyzed whether placental and fetal PPARa 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 PPARa agonists (clofibrate and 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 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 show reduced PPARa concentrations. They present no lipid overaccumulation but reduced lipid synthesis, parameters negatively regulated by PPARa activators. Lipid peroxidation and NO production, increased in placentas from diabetic rats, were negatively regulated by PPARa activators. Fetal PPARa activation in diabetic rats does not change placental lipid concentrations, but reduced placental weight and NO production. In conclusion, PPARa activators regulate lipid metabolism and NO production in term placentas from diabetic rats, an activation that regulates placental growth and can be partly exerted by the developing fetus.