Effects of PPAR activation in the placenta and the fetus: Implications in maternal diabetes.

A. JAWERBAUM

Pasadena, California

Congreso; Congress: Diabetes and Pregnancy Study Group- West 2012 (DPSG-W 2012); 2012

DPSG-W

Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors that regulate metabolic, anti-inflammatory and developmental processes. In maternal diabetes, the maternal metabolic impairments, the intrauterine pro-inflammatory environment and the developmental defects induced make PPARs a relevant focus of investigation. There are three PPAR isoforms: PPARá, PPARã and PPARä, but only the latter is expressed during embryo organogenesis. Experimental models of diabetes and pregnancy show reduced PPARä concentrations and impaired PPARä signalling pathways in embryos during early organogenesis, alterations related to the induction of congenital malformations. In diabetic fetuses, fetal lipid metabolism, lipid peroxidation and several pro-inflammatory markers are regulated by the activation of the three PPAR isotypes. In the diabetic placenta, the activation of the different PPAR isotypes regulates lipid metabolism and anti-inflammatory pathways. There are alterations in the expression of PPARs in placental and fetal tissues from diabetic animals and in the placenta from diabetic patients. Besides, deficiency in polyunsaturated fatty acids (PUFAs) and impaired formation of arachidonic acid derivatives that activate PPARs are observed in diabetic intrauterine tissues. Activation of PPARs can be achieved by both natural and pharmacological activators. Our results show that intrauterine activation of PPARs can be achieved by the administration of maternal diets enriched in olive oil and safflower oil, leading to the regulation of the altered metabolic and pro-inflammatory pathways in the embryo, the fetus and the placenta in experimental models of diabetes and pregnancy.