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. 2023;6(2):56-67.
doi: 10.26502/fjwhd.2644-288400108. Epub 2023 May 4.

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

Jay S Mishra  1 , Sathish Kumar  1   2   3
Affiliations

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

Jay S Mishra et al. J Womens Health Dev. 2023.

Abstract

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.

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

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Conflict of interest statement

Conflicts of interest: None

Figures

Fig 1.
Fig 1.
Changes in (A) fasting glucose, (B) fasting insulin, (C) maternal weight, (D) total maternal weight gain, (E) daily food intake, and (F) daily water intake in pregnant rats treated from GD7 to GD20 with S961 or vehicle. All data are expressed as means ± SE of six dams in each group; ∗P < 0 .05 vs. control.
Fig 2.
Fig 2.
Blood glucose levels and insulin responses following intraperitoneal glucose tolerance test in control and S961-treated rats. Pregnant rats were treated with S961 or vehicle from GD7 to GD20. Following overnight fasting, intraperitoneal glucose tolerance tests were performed on GD19. Blood samples were collected at 0, 30, 60, 90, and 120 min following intraperitoneal glucose (2 g/kg) administration for measurement of (A) plasma glucose and (B) insulin levels. The overall plasma glucose levels and insulin responses are expressed as the AUC calculated by the trapezoidal method (bottom panel). Results are expressed as means ± SE of six dams in each group; ∗P < 0 .05 vs. control.
Fig 3.
Fig 3.
Changes in (A) maternal blood pressure and (B) heart rate in pregnant rats treated from GD7 to GD20 with S961 or vehicle. Mean arterial blood pressure and heart rate were measured using a noninvasive CODA system on GD20. All data are expressed as means ± SE of six dams in each group; ∗P < 0 .05 vs. control.
Fig 4.
Fig 4.
qPCR validation of mRNA expression of genes related to fatty acid β-oxidation and fatty acid transport in the placenta of control and S961 treated dams. mRNA expressions were determined by quantitative RT-PCR, and results were normalized with β-actin. Values are expressed as means ± SE of six dams in each group; ∗P < 0 .05 vs. control.
Fig 5.
Fig 5.
Changes in mRNA levels of genes related to fatty acid transport in the placenta exposed to vehicle and S961. mRNA expressions were determined by quantitative RT-PCR, and results were normalized with β-actin. Values are expressed as means ± SE of six dams in each group; ∗P < 0 .05 vs. control.
Fig 6.
Fig 6.
Possible mechanisms for altered placental lipid processing and LCPUFA transfer in lean GDM condition.
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