Effects of natural ligands of PPARgamma on lipid metabolism in placental tissues from healthy and diabetic rats.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent nuclear receptor that plays an important role in placental development and function metabolism in diabetic and control rats after midpregnancy, as well as the concentrations of the PPARgamma endogenous agonist 15deoxyDelta(12,14)Prostaglandin J(2) (15dPGJ(2)). In vitro experiments showed that 15dPGJ(2) did not regulate placental concentrations of triglycerides, cholesteryl esters, phospholipids and free fatty acids, but decreased the de novo synthesis of these lipid species. PPAR agonists were administered in vivo through dietary supplementation with either 6% olive oil or 6% safflower oil. These treatments led to increases in placental lipid mass in control tissues and more markedly in diabetic tissues. In addition, they led to reductions in the de novo lipid synthesis both in control and in diabetic placental tissues. In the placenta from diabetic rats fed with the standard diet, 15dPGJ(2) concentrations were greatly reduced. Both dietary supplementations increased the concentrations of 15dPGJ(2) in placentas from control and diabetic rats. These data indicate that, in the placenta, PPARgamma natural ligands regulate the concentration of their own endogenous ligands. In addition, they increase the placental capacity to accumulate maternal-derived lipids, and reduce the de novo lipid synthesis, thus regulating metabolic pathways that are altered in the placenta from diabetic rats and involved in the lipid transfer to the developing fetus.