Activation of the nuclear receptors PPARs regulates lipid metabolism in the placenta from diabetic patients.

CAPOBIANCO E,; MARTÍNEZ N,; FORNES D,; HIGA R,; DI MARCO I,; BASUALDO MN

Lille

Congreso; 44th Annual Meeting, Diabetes and Pregnancy Study Group (DPSG), EASD; 2012

Diabetes and Pregnancy Study Group

Maternal diabetes induces metabolic alterations and a pro-oxidant environment in the intrauterine compartment that affect fetal and placental development. Macrosomia and placentomegalia, related to the overaccumulation of metabolic substrates, are found in term pregnancies in pregestational and gestational diabetes. Peroxisome proliferator activated receptors (PPARs) are ligand activated nuclear receptors that regulate lipid metabolism, anti-inflammatory pathways and development. We aimed to evaluate PPARs concentration and lipid concentrations and peroxidation in term placentas from healthy and type 2 diabetic patients as well as to determine whether the activation of each of the three PPAR isotypes regulate lipid concentrations and peroxidation in term placentas from these patients. Placentas were obtained after delivery and processed for evaluation of PPARs by Western blot, of lipids by TLC and of lipid peroxidation by TBARS determination. Placental explants were incubated with natural and pharmacological PPAR activators for further evaluation of lipids concentration and peroxidation. We found decreased concentrations of PPARa and PPARγ, increased concentrations of triglycerides, cholesterol, cholesteryl esters and phospholipids, as well as increased lipid peroxidation in placentas from diabetic patients when compared to controls (P < 0.05). PPARa activators (LTB4 1 μM and clofibrate 20 μM) reduced the concentrations of lipids in healthy and diabetic placentas (P < 0.05). PPARδ activators (cPGI2 1 µM and GW 501516 100nM) reduced the lipid concentrations in the placentas from healthy patients (P < 0.01). PPARγ activators (15deoxydelta12,14PGJ2 2µM and rosiglitazone 3µM) increased the lipids concentrations in placentas from healthy and diabetic patients (P < 0.01). Activation of the three PPAR isotypes led to a reduction in the lipid peroxidation in placentas from diabetic patients (P < 0.05). We conclude that there are important alterations in lipid metabolism and peroxidation in the placentas from type 2 diabetic patients that occur in parallel to changes in PPARs concentrations, nuclear receptors capable of regulating lipid metabolism and peroxidation in the placentas from diabetic patients