Activation of Peroxisome proliferator activated receptors (PPARs) modulates lipid levels and metabolism in the placenta from control and diabetic rats

JAWERBAUM ALICIA; CAPOBIANCO EVANGELINA; MARTÍNEZ NORA; PUSTOVRH CAROLINA; WHITE VERÓNICA; HIGA ROMINA; GONZÁLEZ ELIDA

Cleveland, Ohio.

Congreso; Activation of Peroxisome proliferator activated receptors (PPARs) modulates lipid levels and metabolism in the placenta from control and diabetic rats; 2006

8th Annual Meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA)

PPARs are nuclear receptors involved in lipid homeostasis in different tissues. Maternal diabetes alters lipid metabolism and affects feto-placental development. We aimed to evaluate whether PPARs agonists regulate lipid levels and metabolism in the placenta from control and neonatal-streptozotocin-induced diabetic rats at midgestation. Methods: Placental explants were cultured for 3 h either with or without PPARs agonists: clofibrate (a PPARalpha agonist, 20 mM), 15deoxydelta12,14Prostaglandin J2 (15dPGJ2, a PPARgamma agonist, 2 mM , and carbaprostacyclin (cPGI2, a PPARdelta agonist, 1 mM). The levels of triglycerides (TG), cholesterol (CHOL), cholesteryl esthers (ECHOL) and phospholipids (PL) were evaluated by TLC and densitometry. The de novo lipid synthesis was determined by the incorporation of 14C -acetate to the different lipid classes evaluated. Esterified lipids catabolism was evaluated by the determination of glycerol release to the incubation media. Results: In placenta from diabetic rats (D) we found increased TG (p<0.05) and ECHOL (p<0.01) levels when compared to controls (C). The de novo synthesis of TG (p<0.01), PL (p<0.05), CHOL (p<0.05) and ECHOL (p<0.001) was reduced in D when compared to C. Lipid catabolism was greatly enhanced in D when related to C (p<0.001). In both C and D, the PPARalpha agonist clofibrate diminished the levels of TG, PL and ECHOL (p<0.05). The activation of PPARalpha also enhanced the de novo placental lipid synthesis (p<0.05) and stimulated placental lipid catabolism (p<0.01). Differently, the PPARgamma agonist 15dPGJ2 did not modify lipid levels and lipid catabolism, but significantly reduced the de novo lipid synthesis in both C and D (p<0.05). The activation of PPARdelta by cPGI2 also induced different effects: it reduced both the levels of PL (p<0.05) and the de novo lipid synthesis (p<0.05) in C and D, and resulted in an important enhancement of lipid catabolism (p<0.001) in these tissues. Conclusions: Our findings identified novel roles of the different PPARs isotypes in the regulation of placental lipid levels and metabolism. Due to the significant alterations found in lipid levels and metabolism in the diabetic placenta, this regulatory role of PPARs may contribute in the understanding of possible mechanisms to prevent these anomalies.