Gestational Diabetes Mellitus and mitochondrial metabolism: transcriptional and post-transcriptional alterations and their relationship with newborn obesity predisposition

• Grant number: 14/09957-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2014
• End date: December 31, 2015
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: João Paulo de Castro Marcondes
• Grantee: Pablo Felipe Bertolini Andrade
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Obesity is a multifactorial disease, associated with a range of metabolic disturbances. Environmental factors contribute for BMI (Body Mass Index) variation, however, the genetic background can be also responsible for these variations. Several findings have demonstrated that in utero stressors (such as gestational diabetes, nutritional alteration, etc) can promote transcriptional and post-transcriptional changes, besides affecting mitochondrial metabolism, which could be involved in the etiology of diabetes, obesity and their co-morbities. Furthermore, these alterations could modulate fetal development and predispose to later development of diseases, including obesity and other metabolic syndromes. Therefore, this study aims to identify, in cells from placenta (fetal and maternal sides) and umbilical cord blood of newborns of mothers with gestational diabetes mellitus (GDM), whether certain transcriptional (expression of SIRT1 gene, indirectly related to mitochondrial metabolism) and post-transcriptional events (expression of miR-181a, predict in silico as a putative regulator of SIRT1 gene) are related to a increased risk for developing obesity in adulthood. The study will include pregnant women with GDM (Group 1, n = 15) and their respective newborns (Group 2, n = 15), and healthy pregnant women (Group 3, n = 15) and their newborns (Group 4, n = 15). Additionally, adult obese (Group 5, n = 15) and eutrophic (Group 6, n = 15) subjects will be included as reference populations. It is expected the results may contribute for elucidating molecular changes induced by gestational diabetes that could be related to obesity in adulthood.