PPARδ and its activator PGI2 are reduced in diabetic embryopathy: involvement of PPARδ activation in lipid metabolic and signalling pathways in rat embryo early organogenesis

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Maternal diabetes significantly increases the risk of congenital malformations, and the mechanisms involved are not yet clarified. This study was designed to address peroxisome proliferator-activated receptor δ (PPARδ) involvement in diabetic embryopathy. We investigated the concentrations of PPARδ and its endogenous agonist prostaglandin (PG)I2, as well as the effect of PPARδ activation on lipid metabolism and PGE2 concentrations in embryos from control and streptozotocin-induced diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARδ and its endogenous agonist PGI2 when compared with controls. In embryos from control rats, the addition of the PPARδ activators (cPGI2 and PGA1) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using 14C-acetate as a tracer. PGE2 formed from arachidonate released from phospholipid stores was also up-regulated by PPARδ activators. In embryos from diabetic rats, reduced phospholipid synthesis and PGE2 content were observed, and clearly up-regulated by cPGI2 additions to values similar to those found in control embryos. These data suggest that PPARδ may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARδ and its endogenous activator PGI2.

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