Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism.

INTRODUCTION: Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. MATERIALS AND METHODS: Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. RESULTS: Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. CONCLUSION: Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

Decreased maternal serum adiponectin and increased insulin-like growth factor-1 levels along with increased placental glucose transporter-1 expression in gestational diabetes mellitus: Possible role in fetal overgrowth.

INTRODUCTION: The placental glucose transporter - 1 (GLUT-1) is involved in the transplacental glucose transport to the fetus. GLUT-1 expressions are increased in diabetic pregnancies and associated with altered fetal growth. However, the factors regulating the GLUT-1 expressions are largely unknown. We hypothesised that maternal adipokines and insulin-like growth factor-1 (IGF1) modulate the placental expressions of GLUT-1 through the activation of insulin/IGF-1 signalling which may contribute to a fetal overgrowth in GDM. METHODS: Maternal blood, cord blood and placental samples were collected from GDM and control pregnant women (CPW). The biochemical parameters, IGF1, adipokines, and high sensitive C- reactive protein were measured. We analysed the placental expressions of GLUT-1 and proteins related to insulin/IGF-1 signalling - insulin receptor -ß, insulin receptor substrate - 1, phosphatidylinositol-3-kinase p110α, phospho Akt-1, phospho extracellular signal-regulated kinase 1/2, and nuclear factor-κB p65 in GDM and CPW. RESULTS: Increased maternal IGF-1 and decreased adiponectin levels were found in the GDM women. Maternal IGF-1 levels were positively correlated, whereas adiponectin levels were negatively correlated with the birth weight of GDM newborns. Increased phosphorylation of Akt and ERK 1/2 was found in the placenta of GDM women. Placental expressions of GLUT-1 were significantly higher in the GDM women and positively correlated to the maternal IGF-1 levels in the GDM group. DISCUSSION: Decreased maternal adiponectin and increased IGF-1 levels might have caused increased GLUT-1 expression via the increased activation of insulin/IGF-1 signalling in the placenta of GDM women which might have influenced the fetal growth.