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Myo-inositol moderates glucose-induced effects on human placental 13C-arachidonic acid metabolism

Myo-inositol moderates glucose-induced effects on human placental 13C-arachidonic acid metabolism
Myo-inositol moderates glucose-induced effects on human placental 13C-arachidonic acid metabolism

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.

LCMS, diabetes, lipid, metabolism, pregnancy
2072-6643
Watkins, Oliver C.
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Cracknell-Hazra, Victoria K.B.
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Pillai, Reshma Appukuttan
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Selvam, Preben
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Yong, Hannah E.J.
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Sharma, Neha
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Patmanathan, Sathya Narayanan
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Cazenave-Gassiot, Amaury
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Bendt, Anne K.
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Godfrey, Keith
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Lewis, Rohan
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Wenk, Markus R.
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Chan, Shiao-Yng
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Watkins, Oliver C.
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Cracknell-Hazra, Victoria K.B.
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Pillai, Reshma Appukuttan
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Selvam, Preben
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Yong, Hannah E.J.
9d6a310c-8309-4d94-9dd2-7766cb0420ac
Sharma, Neha
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Patmanathan, Sathya Narayanan
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Cazenave-Gassiot, Amaury
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Bendt, Anne K.
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Godfrey, Keith
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Lewis, Rohan
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Wenk, Markus R.
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Chan, Shiao-Yng
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Watkins, Oliver C., Cracknell-Hazra, Victoria K.B., Pillai, Reshma Appukuttan, Selvam, Preben, Yong, Hannah E.J., Sharma, Neha, Patmanathan, Sathya Narayanan, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith, Lewis, Rohan, Wenk, Markus R. and Chan, Shiao-Yng (2022) Myo-inositol moderates glucose-induced effects on human placental 13C-arachidonic acid metabolism. Nutrients, 14 (19), [3988]. (doi:10.3390/nu14193988).

Record type: Article

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.

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Accepted/In Press date: 22 September 2022
Published date: 26 September 2022
Keywords: LCMS, diabetes, lipid, metabolism, pregnancy

Identifiers

Local EPrints ID: 472335
URI: http://eprints.soton.ac.uk/id/eprint/472335
ISSN: 2072-6643
PURE UUID: 9bc04c6a-a0d3-453a-9a60-0b7d990ae840
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Rohan Lewis: ORCID iD orcid.org/0000-0003-4044-9104

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Date deposited: 01 Dec 2022 17:45
Last modified: 17 Mar 2024 02:53

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Contributors

Author: Oliver C. Watkins
Author: Victoria K.B. Cracknell-Hazra
Author: Reshma Appukuttan Pillai
Author: Preben Selvam
Author: Hannah E.J. Yong
Author: Neha Sharma
Author: Sathya Narayanan Patmanathan
Author: Amaury Cazenave-Gassiot
Author: Anne K. Bendt
Author: Keith Godfrey ORCID iD
Author: Rohan Lewis ORCID iD
Author: Markus R. Wenk
Author: Shiao-Yng Chan

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