27: Maternal inositol supplementation modulates placental metabolic programming in a pregnant murine model of metabolic syndrome

Abstract

Metabolic syndrome (MS) and hypertension (HTN) in pregnancy impact offspring health in adult life. We showed that offspring born to MS dams have an altered metabolic phenotype that was improved by maternal inositol (INO) supplementation. Our objective was to test the hypothesis that the beneficial effect of INO is mediated through placental metabolic pathways in offspring born to a murine model of MS. Female heterozygous for endothelial nitric oxide synthase gene (eNOS-/+) with hypertension were placed on control (HTN) or high-fat diet for 4 wks to induce a MS phenotype, then bred with wild-type male. On gestational day 1, dams with MS were allocated to receive INO (MS-INO) or water (MS). Three groups were obtained: HTN, MS, and MS-INO. Dams were euthanized at term. Placental biopsy from fetal side were genotyped for eNOS allele and gender. Male (M-PL) and female (F-PL) eNOS-/+ placenta were selected. Glycogen (Gly) was measured by ELISA. Proteins involved in glucose uptake (GLUT4 and IR-β), glycogen synthesis (Akt, pAktT-308 and GSK3), and ATP production (pPDH) were measured using Western blot. 1-way or 2-way ANOVA were used for statistical analysis. Gly was higher in M-PL and F-PL of MS dams vs. HTN dams, and reduced by INO supplementation (Fig. 1A). GLUT4 was higher in M-PL of MS vs. HTN and INO treated dams; no differences were seen in female (Fig. 1B). pPDH was reduced in placenta of M-PL and F-PL of HTN and MS dams, and was increased by INO supplementation (Fig. 1C). IR-β was higher in M-PL vs. F-PL. Akt was not different between groups in either gender. Active pAktT-308 was higher in F-PL from MS vs. HTN dams and was lowered by INO treatment, but no differences were noted in M-PL. GSK3 was higher in M-PL and F-PL of HTN and MS dams and was lowered by INO (Table 1). MS during pregnancy affects offspring placental glucose metabolism by altering its storage and utilization. Male and female adapt differently to those maternal metabolic abnormalities. INO supplementation in MS dams enhances placental glucose use for energy production.View Large Image Figure ViewerDownload Hi-res image Download (PPT)