Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth

TLDR

Maternal obesity elevates placental amino‑acid transporter activity, hinting at a mechanism for fetal overgrowth. The study sought to determine whether maternal obesity up‑regulates placental nutrient transporters, thereby contributing to fetal overgrowth, using a novel mouse model. Female C57BL/6J mice were fed a high‑fat/high‑sugar diet with sucrose, mated, and examined at embryonic day 18.5 to assess maternal and placental changes. Maternal obesity raised insulin, leptin, and cholesterol, lowered adiponectin, increased fetal weight by 18%, and up‑regulated placental GLUT1/3, SNAT2, LAT1 expression and amino‑acid transporter activity.

Abstract

To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested.C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5.HF/HS diet increased maternal fat mass by 2.2-fold (P < 0.01) and resulted in glucose intolerance with normal fasting glucose. Maternal circulating insulin, leptin, and cholesterol were increased (P < 0.05) whereas total and high-molecular-weight adiponectin was decreased (P < 0.05). HF/HS diet increased fetal weight (+18%, P = 0.0005). In trophoblast plasma membranes (TPM) isolated from placentas of HF/HS-fed animals, protein expression of glucose transporter (GLUT) 1 and 3, sodium-coupled neutral amino acid transporter (SNAT) 2, and large neutral amino acid transporter 1 (LAT1) was increased. TPM System A and L amino acid transporter activity was increased in the HF/HS group.Up-regulation of specific placental nutrient transporter isoforms may constitute a mechanism underlying fetal overgrowth in maternal obesity.