Programming of neonatal adipose tissue by maternal gestational diabetes

There is ample evidence linking gestational diabetes melitus (GDM) in utero with offspring obesity and the development of metabolic diseases later in life. Experimental evidence shows that GDM alters DNA methylation of placental and fetal cells. In addition, GDM alters the function of umbilical cord mesenchymal stem cells. However, nothing is known to date about the effects of GDM on MSC and MSC-derived adipocyte programming and resulting adipocyte (dys)function. The proposed project aims to fill this knowledge gap and determine whether GDM in pregnancy shapes the predisposition to obesity and dysfunctional adipose tissue in offspring through epigenetic programming of fetal MSC. Hypothesis: The intrauterine GDM environment reprograms fetal MSC and alters their function and differentiation capacity. This programming affects adipogenesis and stem cell-derived adipocytes in terms of paracrine activity, lipid composition, and insulin resistance. The main goal of this project is to uncover the programming effects of GDM on neonatal MSC and the resulting differential adipogenesis and adipocyte function. Specifically, we aim to determine the effects of maternal GDM on MSC and on differentiated MSC-derived adipocytes in terms of DNA methylation, the secretome, and its effects on angiogenesis, lipid and ganglioside composition, and insulin resistance.