Fetal activation of PPAR alpha: metabolic effects in fetal liver and the placenta

MARTÍNEZ NORA; KURTZ MELISA; WHITE VERÓNICA; JAWERBAUM ALICIA

Santiago de Chile, Chile

Congreso; IFPA Meeting; 2010

International Federation of Placenta Association

Maternal diabetes induces alterations in lipid and nitric oxide (NO) metabolism and affects feto-placental development and growth. PPARa is a nuclear receptor involved in lipid homeostasis in different tissues. Objective: To analyze whether fetal PPARá activation regulate lipid and NO metabolism in the placenta and fetal liver from diabetic rats, and its involvement the feto-placental growth. Methods: Diabetes was induced  by neonatal streptozotocin administration. Fetuses from control and diabetic rats were injected through the uterine wall with the PPARá agonist leukotriene B4 (LTB4, 0.1ìM) on days 19, 20, and 21 of gestation. On day 21 of gestation, placental and fetal liver concentrations of lipids, lipoperoxides and NO were evaluated.  Results: Fetuses and placenta from diabetic rats showed increased weight (p<0.05). In diabetic animals, overaccumulation of triglycerides and cholesteryl esters was observed in the fetal liver (p<0.05), an increase of  lipid peroxidation  was observed in both the placenta and the fetal liver (p<0.01), and an increase in NO production was observed in the fetal liver.  In diabetic animals, fetal treatment with LTB4 reduces the placental, fetal and fetal liver weight (p<0.05). This fetal treatment reduced the concentrations of triglycerides, cholesteryl esters and phospholipids (p<0.05), as well as lipid peroxidation, and NO production in the fetal liver (p<0.01). In addition, it reduced NO production (p<0.05) but did not alter lipid concentrations in the placenta. Conclusions: Our results provide evidence of a fetal role of PPARa activation in the regulation of both lipid homeostasis in the fetal liver and NO production in the fetal liver and the placenta, with an overall impact in fetal and placental growth.