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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental ¹³C-Arachidonic Acid Metabolism.

ABSTRACT: Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with ¹³C-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 µM). Newly synthesized ¹³C-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of ¹³C-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of ¹³C-AA-triacylglycerides (TGs) relative to total placental ¹³C-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four ¹³C-AA-phospholipids and eleven ¹³C-AA-TGs, whilst 17 mM glucose increased ¹³C-AA-PC-40:8 and ¹³C-AA-LPC. Glucose-induced alterations in all ¹³C-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 µM myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications.

SUBMITTER: Watkins OC

PROVIDER: S-EPMC9572372 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental <sup>13</sup>C-Arachidonic Acid Metabolism.

Watkins Oliver C OC Cracknell-Hazra Victoria K B VKB Pillai Reshma Appukuttan RA Selvam Preben P Yong Hannah E J HEJ Sharma Neha N Patmanathan Sathya Narayanan SN Cazenave-Gassiot Amaury A Bendt Anne K AK Godfrey Keith M KM Lewis Rohan M RM Wenk Markus R MR Chan Shiao-Yng SY

Nutrients 20220926 19

Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (<i>n</i> = 19) from women who underwent a mid-gestation ...[more]

PMID: 36235641

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Project description:Well-regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo-inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope-labelled 13 C-PA or 13 C-OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo-inositol (0.3, 30, 60 μm). Forty-seven 13 C-PA lipids and 37 13 C-OA lipids were measured by liquid chromatography-mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 13 C-OA lipids and nine 13 C-PA lipids, but decreased 13 C-OA phosphatidylethanolamine 38:5 and 13 C-PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13 C-OA acylcarnitine 18:1, and insulin increasing four 13 C-PA triacylglycerides. Most glucose, leptin and insulin-induced alterations in lipids were attenuated by co-incubation with myo-inositol (30 or 60 μm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose-induced increases in acylcarnitine were not attenuated by myo-inositol and were even exaggerated in some instances. Myo-inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo-inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. KEY POINTS: Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13 C-lipids from 13 C-palmitic acid (PA) and 13 C-oleic acid (OA) in vitro compared with untreated controls from the same placenta. Co-incubation with myo-inositol attenuated most alterations induced by glucose, insulin or leptin in 13 C-lipids, but did not affect alterations in 13 C-acylcarnitines. Alterations induced by glucose and leptin in 13 C-PA triacylglycerides and 13 C-PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo-inositol co-incubation. Insulin differently affected 13 C-PA triacylglycerides and 13 C-PA phospholipids depending on fetal sex, with alterations also attenuated by myo-inositol co-incubation.

Project description:Inositol phospholipids in cultured GH3 cells, a prolactin secreting, thyrotropin-releasing hormone (TRH) sensitive rat pituitary cell line, exhibit a preferential selectivity for incorporating arachidonic acid. Fatty acid composition data show that all inositol phospholipids are enriched in stearic and arachidonic acids to a much greater degree than other cellular phospholipids. Incubation of GH3 cells with radioactive stearate, oleate, arachidonate, eicosapentaenoate or docosahexaenoate also showed that much more stearate and arachidonate were incorporated into inositol phospholipids. In short term incubations with tracer amounts of radioactive arachidonate, incorporation was initially into phosphatidylinositol (PtdIns), with phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] being labelled at later times. During longer incubations, all of the inositol phospholipids reach equilibrium at about 10 h, and the resulting specific activities of the three fractions were similar. These findings suggest that arachidonate is incorporated initially into PtdIns and that PtdIns is then phosphorylated. There was no release of either arachidonate or eicosanoid products when GH3 cells were incubated with TRH. However, TRH stimulation of 32P-labelled GH3 cells resulted in rapid breakdown of PtdIns(4,5)P2 and PtdIns4P, with concomitant increases in [32P]phosphatidic acid and [32P]PtdIns. When the [32P]PtdIns was further analysed by argentation chromatography to separate PtdIns molecular species, it was found that tetraenoic (stearate/arachidonate) species accounted for 80% of the stimulated labelling. The selectivity for arachidonate incorporation into inositol phospholipids coupled with turnover of the arachidonate-containing molecular species suggests that inositol phospholipids containing arachidonic acid or the diacylglycerol resulting therefrom may play a vital cellular role in GH3 cells. This role may involve the operation of the PtdIns cycle itself rather than a stimulated release of arachidonate for eicosanoid formation.

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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental ¹³C-Arachidonic Acid Metabolism.

Publications

Myo-Inositol Moderates Glucose-Induced Effects on Human Placental <sup>13</sup>C-Arachidonic Acid Metabolism.

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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism.

Publications

Myo-Inositol Moderates Glucose-Induced Effects on Human Placental <sup>13</sup>C-Arachidonic Acid Metabolism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental ¹³C-Arachidonic Acid Metabolism.