PPARs activation in maternal diabetes: Fetal effects

JAWERBAUM A

Simposio; SLIMP Satellite; 2014

Embryo and fetal development is affected by maternal diabetes, alterations related to the intrauterine programming of metabolic diseases. PPARs are ligand activated transcription factors that regulate metabolic, anti-inflammatory and developmental processes. There are three PPAR isoforms: PPARalfa, PPARgamma and PPARdelta, and the three of them expressed in the fetus and only PPARdelta expressed in the embryo during early organogenesis. Experimental models of diabetes and pregnancy show reduced PPARdelta concentrations and impaired PPARdelta 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. 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 and the fetus. Moreover, these maternal treatments have also an impact in the offspring, as that they also can prevent the intrauterine programming of heart metabolic alterations.