Premio "John Stowers Award to Best Poster Presentantion" al trabajo "Peroxisome Proliferator activated receptor alpha (PPARalpha) agonists modulate lipid metabolism in the feto-placental unit from control and diabetic rats."

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

Ibiza, España

Congreso; 39th Annual Meeting, Diabetes and Pregnancy Study Group (DPSG), EASD.; 2007

Diabetes and Pregnancy Study Group, EASD

Maternal diabetes induces alterations in lipid metabolism and affects feto-placental development and growth. PPARa is a nuclear receptor involved in lipid homeostasis in different tissues. Objective: To analyze whether PPAR agonists regulate lipid metabolism in the placenta and fetuses from control (C) and neonatal-streptozotocin-induced diabetic rats (D).  Methods: Fetuses and placenta (day 13 of gestation) were cultured 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. Glycerol release to the incubation media was analyzed as an index of lipid catabolism. PPARa protein expression was measured by western blot. Results: In C placenta, clofibrate reduced cholesteryl esters (ECHOL, 46%, p<0.05),  triglycerides (TG, 43%, p<0.05) and phospholipids (PL, 63%, p<0.01), while LTB4 did not change the levels of the studied lipids. In D placenta, where both TG (50%, p<0.05) and ECHOL (93%, p<0.01) are increased when compared to C tissues, LTB4 negatively regulated the concentrations of cholesterol (CHOL, 20%, p<0.05) and PL (48%, p<0.05); whereas clofibrate reduced the levels of all the lipids evaluated (p<0.05). Glycerol release was increased in D placenta when related to C (99%, p<0.001), and was also increased in C placentas incubated in the presence of the PPARa agonists C (133% p<0.01). D placenta showed increased protein expression of PPARa (300%, p<0.01) when compared to C. When the fetuses were studied, we observed an increase in PL concentrations (52%, p<0.01) in fetuses from D mothers when compared to C. The studied PPARa agonists reduced  (p<0.05) the concentrations of TG, ECHOL and CHOL in fetuses from both C and D rats. Conclusions: Our results provide evidence of a novel role of PPARa as a modulator of lipid metabolism in both fetuses and placenta. Alterations in PPARa concentrations probably leads to alterations in the metabolism of lipids in the feto-placental unit from diabetic pregnancies.