PPARs and diabetes in pregnancy.

JAWERBAUM A

Workshop; International Postgraduate Workshop on Pregnancy Diseases (IPW). Vascular Dysfunction Mechanisms.; 2012

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: PPARα, PPARγ and PPARδ, but only the latter is expressed during embryo organogenesis. Experimental models of diabetes in pregnancy show reduced PPARδ concentrations and impaired PPARδ signaling pathways in embryos during early organogenesis, alterations related to the induction of congenital malformations. The three PPAR isotypes are expressed and relevant in the placenta, and there are alterations in the expression of PPARα and PPARγ in the placenta from experimental models of diabetes and from diabetic patients. PPARs activation in the placenta has relevant function in the regulation of lipid metabolism, nitric oxide production and matrix metalloproteinases activities. In fetuses from diabetic rats, lipid metabolism, lipid peroxidation and several pro-inflammatory markers are regulated by the activation of the three PPAR isotypes. Deficiency in polyunsaturated fatty acids (PUFAs) and impaired formation of arachidonic acid derivatives that activate PPARs are observed in diabetic intrauterine tissues. There is an efficient transfer of lipids through the placenta, and maternal treatments enriched in unsaturated fatty acids are capable of activating PPARs in embryos, fetuses and placentas. Our results show that the intrauterine activation of PPARs leads to the regulation of impairments in lipid homeostasis, pro-inflammatory pathways and growth in placentas and fetuses from experimental models of diabetes in pregnancy.