Increased glucose and placental GLUT-1 in large infants of obese nondiabetic mothers.

Obese women are at increased risk to deliver a large infant, however, the underlying mechanisms are poorly understood. Fetal glucose availability is critically dependent on placental transfer and is linked to fetal growth by regulating the release of fetal growth hormones such as insulin. We hypothesized that (1) umbilical vein glucose and insulin levels and (2) placental glucose transporter (GLUT) expression and activity are positively correlated with early pregnancy maternal body mass index and infant birthweight. Subjects in this prospective observational cohort study were nondiabetic predominantly Hispanic women delivered at term. Fasting maternal and umbilical vein glucose and insulin concentrations were determined in 29 women with varying early pregnancy body mass index (range, 18.0-54.3) who delivered infants with birthweights ranging from 2800-4402 g. We isolated syncytiotrophoblast microvillous and basal plasma membranes from 33 placentas and determined the expression of GLUT-1 and -9 (Western blot) and glucose uptake (radiolabeled glucose). Birthweight was positively correlated with umbilical vein glucose and insulin and maternal body mass index. Umbilical vein glucose levels were positively correlated with placental weight and maternal body mass index, but not with maternal fasting glucose. Basal plasma membranes GLUT-1 expression was positively correlated with birthweight. In contrast, syncytiotrophoblast microvillous GLUT-1 and -9, basal plasma membranes GLUT-9 expression and syncytiotrophoblast microvillous and basal plasma membranes glucose transport activity were not correlated with birthweight. Because maternal fasting glucose levels and placental glucose transport capacity were not increased in obese women delivering larger infants, we speculate that increased placental size promotes glucose delivery to these fetuses.

Acosta O ，Ramirez VI ，Lager S ，Gaccioli F ，Dudley DJ ，Powell TL ，Jansson T ... -  《-》

Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies.

Jansson N ，Rosario FJ ，Gaccioli F ，Lager S ，Jones HN ，Roos S ，Jansson T ，Powell TL ... -  《-》

Uteroplacental Glucose Uptake and Fetal Glucose Consumption: A Quantitative Study in Human Pregnancies.

Michelsen TM ，Holme AM ，Holm MB ，Roland MC ，Haugen G ，Powell TL ，Jansson T ，Henriksen T ... -  《-》

Maternal glucagon-like peptide-1 is positively associated with fetal growth in pregnancies complicated with obesity.

Pregnant women with obesity are more likely to deliver infants who are large for gestational age (LGA). LGA is associated with increased perinatal morbidity and risk of developing metabolic disease later in life. However, the mechanisms underpinning fetal overgrowth remain to be fully established. Here, we identified maternal, placental, and fetal factors that are associated with fetal overgrowth in pregnant women with obesity. Maternal and umbilical cord plasma and placentas were collected from women with obesity delivering infants who were LGA (n=30) or appropriate for gestational age (AGA, n=21) at term. Maternal and umbilical cord plasma analytes were measured using multiplex sandwich assay and ELISA. Insulin/mechanistic target of rapamycin (mTOR) signaling activity was determined in placental homogenates. Amino acid transporter activity was measured in isolated syncytiotrophoblast microvillous membrane (MVM) and basal membrane (BM). Glucagon-like peptide-1 receptor (GLP-1R) protein expression and signaling were measured in cultured primary human trophoblast (PHT) cells. Maternal plasma glucagon-like peptide-1 (GLP-1) was higher in LGA pregnancies and positively correlated to birthweight. Umbilical cord plasma insulin, C-peptide, and GLP-1 were increased in obese-large for gestational age (OB-LGA) infants. LGA placentas were larger but showed no change in insulin/mTOR signaling or amino acid transport activity. GLP-1R protein was expressed in the MVM isolated from human placenta. GLP-1R activation stimulated protein kinase alpha (PKA), extracellular signal-regulated kinase-1 and-2 (ERK1/2), and mTOR pathways in PHT cells. Our results suggest elevated maternal GLP-1 may drive fetal overgrowth in obese pregnant women. We speculate that maternal GLP-1 acts as a novel regulator of fetal growth by promoting placental growth and function.

Dumolt JH ，Rosario FJ ，Kramer AC ，Horwitz S ，Powell TL ，Jansson T ... -  《-》

Changes in Placental Nutrient Transporter Protein Expression and Activity Across Gestation in Normal and Obese Women.

James-Allan LB ，Teal S ，Powell TL ，Jansson T ... -  《-》