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.

Myo‐inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism

“…In vitro myo‐inositol treatment of placental explants has been found to moderate maternal glycaemia and body mass index (BMI)‐associated variations in placental docosahexaenoic acid (DHA) metabolism (Watkins et al., 2022b ) and to attenuate the effects of in vitro glucose on placental arachidonic acid (AA) metabolism (Watkins et al., 2022a ). However, nothing is known about how myo‐inositol affects the placental metabolism of saturated or monosaturated fatty acids, despite palmitic acid (PA, saturated) and oleic acid (OA, monounsaturated) comprising the majority of maternal, fetal and placental lipids (Herrera, 2000 ).…”