Placental Fatty Acid Metabolism and Transport in a Rat Model of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a form of heightened Insulin resistance triggered during gestation. This study examines how Insulin resistance alters placental long-chain polyunsaturated fatty acid (LCPUFA) transport and metabolism in a rat model of lean GDM. Pregnant Sprague Dawley rats were administered with S961, an Insulin Receptor antagonist (30 nmol/kg s.c. daily), or vehicle from gestational day (GD) 7 to 20. Daily maternal body weight, food, and water intake were measured. Blood pressure assessment and glucose tolerance test were done on GD20. Fetal plasma and placenta were collected on GD20 and processed for fatty acid measurement using LC-mass spectrometry. The expression of fatty acid metabolism-related genes in the placenta was assessed using RT² Profiler PCR arrays. The results were validated by qRT-PCR. Blockade of Insulin receptors with S961 in pregnant rats resulted in glucose intolerance with increased fasting glucose and Insulin levels. Maternal body weight gain and food and water intake were not affected; however, S961 significantly increased maternal blood pressure and heart rate. The placenta n3 and n6 LCPUFA concentrations were significantly decreased by 8% and 11%, respectively, but their levels in the fetal plasma were increased by 15% and 4%. RT2 profiler arrays revealed that placental expressions of 10 genes related to fatty acid β-oxidation (Acaa1a, Acadm, Acot2, Acox2, Acsbg1, Acsl4, Acsm5, Cpt1b, Eci2, Ehhadh) and 3 genes related to fatty acid transport pathway (Fabp2, Fabp3, Slc27a3) were significantly upregulated. In summary, lack of Insulin action increased the expression of genes related to placental fatty acid β-oxidation and transport with an increased transfer of LCPUFA to the fetus. The increased lipid levels routed toward the fetus may lead to fat adiposity and later-life metabolic dysfunction.

Fatty Acid; Gestational Diabetes; Insulin Resistance; Placenta; Pregnancy.