Altered lipid levels in the feto-placental unit from diabetic rats: modulatory effects of the peroxisome proliferator activated receptor alpha (PPARalpha) agonists.

JAWERBAUM A; MARTÍNEZ N; CAPOBIANCO E; PUSTOVRH C; WHITE V; HIGA R; GONZÁLEZ E

Santiago de Chile

Simposio; II Latin-American Symposium Materno-Fetal Interaction and Placenta: From Basic to Clinical Research (SLIMP). Internacional Federation of Placental Associations (IFPA), Placenta Association of the Americas (PAA); 2005

SLIMP

Diabetes induces alterations in maternal lipid metabolism and affects feto-placental  development. PPARa is a nuclear receptor involved in lipid homeostasis in different tissues. We aimed to evaluate the levels of triglycerides (TG), cholesterol (CHOL), cholesteryl esthers (ECHOL) and phospholipids (PL) and to determine whether PPARa agonists regulate lipid metabolism in the feto-placental unit from control (C) and neonatal-streptozotocin-induced diabetic rats (D).  Methods: Fetuses and placenta (day 13.5 of gestation) were incubated for 3 h either with or without LTB4 (an endogenous PPARa agonist,  0.1 mM) or clofibrate (a pharmacological PPARa agonist, 20 mM). Lipids were evaluated by TLC and densitometry. LTB4 was measured by EIA. Results: In D placenta we found increased TG (50%, p<0.05) and ECHOL (93%, p<0.01) levels when compared to C. In C placenta, no effects of PPARa agonists on lipid levels were found. In D placenta, LTB4 reduced CHOL (21%, p<0.05) and PL (47%, p<0.02) levels and clofibrate reduced levels of all lipids evaluated (p<0.05). In D fetuses, there were increased PL levels (138%, p<0.01) when compared to C, while CHOL, ECHOL and TG levels remained unaltered. PPARa agonists reduced (p<0.05) CHOL, ECHOL and TG levels and did not modify PL levels in C and D fetuses. LTB4 levels were reduced in D fetuses (58%, p<0.05) and placenta (82%, p<0.01) when compared to C. Conclusions: Our results provide evidence of a novel role of PPARa in the regulation of lipid levels in the feto-placental unit. LTB4 is reduced in D fetuses and placenta and is likely to be an important regulator of lipid levels in these tissues.