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

Nutrients

10.3390/nu14193988

https://doi.org/10.3390/nu14193988

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

placenta, lipid metabolism, arachidonic acid, inositol, maternal glycaemia

26 September 2022

Watkins, O. C., Cracknell-Hazra, V. K. B., Pillai, R. A., Selvam, P., Yong, H. E. J., Sharma, N., Patmanathan, S. N., Cazenave-Gassiot, A., Bendt, A. K., Godfrey, K. M., Lewis, R. M., Wenk, M. R., & Chan, S.-Y. (2022). Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism. Nutrients, 14(19), 3988. https://doi.org/10.3390/nu14193988

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.

Attribution 4.0 International (CC BY 4.0)

This research is supported by a Clinician Scientist Award awarded to SYC from the Singapore National Medical Research Council (NMRC/CSA-INV/0010/2016; MOH-CSAINV19nov-0002), by the National University of Singapore, National University Health System Singapore and the Singapore Institute for Clinical Sciences A*STAR. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20004)), the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP). The Singapore Lipidomics Incubator receives funding from the Life Sciences Institute, the National University of Singapore Yong Loo Lin School of Medicine and the National Research Foundation (grant number NRFI2015-05).

https://oar.a-star.edu.sg/communities-collections/articles/21987

2072-6643

Institute for Human Development and Potential

https://doi.org/10.3390/nu14193988