Placental mTOR signalling in metabolic diseases

E CAPOBIANCO

Puerto Varas

Congreso; VII SLIMP Latin American Symposium on Maternal Fetal Interaction and Placenta; 2017

The placenta is a metabolic active tissue that not only regulates the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation, but also can adapt morphologically and functionally to optimize substrate supply, and thus fetal growth under adverse intrauterine conditions.Mechanistic target of rapamycin (mTOR) play a central role in placental nutrient sensing and fetal growth. mTOR exists as two different protein complexes, mTOR Complex 1(mTORC1) and mTORC2. The two mTOR complexes have distinct physiological functions and are regulated differently. The dysregulation in the placental mTORC signaling pathways has been related to the development of multiple human pathologies such as cancer, type 2 diabetes and obesity.Children whose mothers had diabetes during pregnancy are at increased risk of becoming obese and developing diabetes at young ages. Besides, any if these female offspring already have diabetes or abnormal glucose tolerance by the time they reach their reproduction age, prolonging the cycle of diabetes. There is some evidence that epigenetic and phenotypic traits induced by early life environment can be passed from one generation to the next.We have recently found that maternal diets enriched in n6/n3 PUFAs in the F0 generation can regulate intrauterine programming of metabolic and placental alterations in their offspring F1 that develops GDM. The regulation of fetal weight and placental mTORC pathways in the next generation highlights the potential use of diets enriched in n6/n3 PUFAs to prevent transgenerational adverse effects of maternal diabetes.