Carbaprostacyclin, a PPARδ agonist, ameliorates excess lipid accumulation in diabetic rat placentas

AimsMaternal 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 PPARδ and its endogenous agonist prostacyclin (PGI2), as well as the effects of carbaprostacylin (cPGI2, a PPARδ agonist) on lipid metabolism in placentas from control and streptozotocin-induced diabetic rats on day 13.5 of gestation.Main methodsThe placentas were explanted to evaluate PPARδ expression and PGI2 concentrations, and cultured with cPGI2 for further analysis of lipid metabolism (concentrations and 14C-acetate derived synthesis of triglycerides, cholesteryl esters, phospholipids, cholesterol and free fatty acids; release of glycerol and lipid peroxidation).Key findingsReduced 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 PPARδ and acyl-CoA oxidase expression, which are changes possibly involved in the catabolic effects observed.SignificanceThe present study reveals the capability of cPGI2 to regulate placental lipid metabolism and PPARδ expression, and suggests that preserving appropriate PGI2 concentrations in the placenta may help to metabolize maternal derived lipid overload in diabetic gestations.