AIMS: Maternal diabetes impairs placental development and metabolism. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors relevant in metabolic homeostasis. We investigated the concentrations of PPARdelta and its endogenous agonist prostacyclin (PGI2), as well as the effects of carbaprostacylin (cPGI(2,) a PPARdelta agonist) on lipid metabolism in placentas from control and streptozotocin-induced diabetic rats on day 13.5 of gestation. MAIN METHODS: The placentas were explanted to evaluate PPARdelta expression and PGI2 concentrations, and cultured with cPGI2 for further analysis of lipid metabolism (concentrations and (14)C-acetate derived synthesis of triglycerides, cholesteryl esters, phospholipids, cholesterol and free fatty acids; release of glycerol and lipid peroxidation). KEY FINDINGS: Reduced PGI2 concentrations were found in the placentas from diabetic rats when compared to controls. cPGI2 additions reduced the concentrations and synthesis of several lipid species, increased lipid catabolism and reduced lipid peroxidation in the placenta. These effects were more marked in diabetic tissues, which presented alterations in the lipid metabolic parameters evaluated. cPGI2 additions increased placental PPARdelta and acyl-CoA oxidase expression, which are changes possibly involved in the catabolic effects observed. SIGNIFICANCE: The present study reveals the capability of cPGI2 to regulate placental lipid metabolism and PPARdelta expression, and suggests that preserving appropriate PGI2 concentrations in the placenta may help to metabolize maternal derived lipid overload in diabetic gestations.
AIMS: Maternal diabetes impairs placental development and metabolism. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors relevant in metabolic homeostasis. We investigated the concentrations of PPARdelta and its endogenous agonist prostacyclin (PGI2), as well as the effects of carbaprostacylin (cPGI(2,) a PPARdelta agonist) on lipid metabolism in placentas from control and streptozotocin-induced diabeticrats on day 13.5 of gestation. MAIN METHODS: The placentas were explanted to evaluate PPARdelta expression and PGI2 concentrations, and cultured with cPGI2 for further analysis of lipid metabolism (concentrations and (14)C-acetate derived synthesis of triglycerides, cholesteryl esters, phospholipids, cholesterol and free fatty acids; release of glycerol and lipid peroxidation). KEY FINDINGS: Reduced PGI2 concentrations were found in the placentas from diabeticrats when compared to controls. cPGI2 additions reduced the concentrations and synthesis of several lipid species, increased lipid catabolism and reduced lipid peroxidation in the placenta. These effects were more marked in diabetic tissues, which presented alterations in the lipid metabolic parameters evaluated. cPGI2 additions increased placental PPARdelta and acyl-CoA oxidase expression, which are changes possibly involved in the catabolic effects observed. SIGNIFICANCE: The present study reveals the capability of cPGI2 to regulate placental lipid metabolism and PPARdelta expression, and suggests that preserving appropriate PGI2 concentrations in the placenta may help to metabolize maternal derived lipid overload in diabetic gestations.
Authors: J M Salbaum; C Kruger; X Zhang; N Arbour Delahaye; G Pavlinkova; D H Burk; C Kappen Journal: Diabetologia Date: 2011-04-14 Impact factor: 10.122