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

OBJECTIVE: To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, we developed a unique mouse model of maternal obesity associated with fetal overgrowth and tested the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity. METHODS: 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. RESULTS: 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 (HMW) adiponectin were decreased (p<0.05). HF/HS diet increased fetal weight (+18%, p=0.0005). In trophoblast plasma membrane (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 transporters 1 (LAT1) was increased. TPM System A and L amino acid transporter activity was increased in the HF/HS group. CONCLUSION: Up-regulation of specific placental nutrient transporter isoforms may constitute a mechanism underlying fetal overgrowth in maternal obesity.