Myo-inositol alters C-labelled fatty acid metabolism in human placental explants

Abstract

We postulate that myo-inositol, a proposed intervention for gestational-diabetes, affects transplacental lipid supply to the fetus. We investigated the effect of myo-inositol on fatty-acid processing in human placental-explants from uncomplicated pregnancies. Explants were incubated with 13C-labeled palmitic-acid, 13C-oleic-acid and 13C-docosahexaenoic-acid across a range of myo-inositol concentrations for 24 h and 48 h. The incorporation of labeled-fatty-acids into individual lipids was quantified by liquid-chromatography-mass-spectrometry. At 24 h, myo-inositol increased the amount of 13C-palmitic-acid and 13C-oleic-acid labeled lipids (median fold-change relative to control=1). Significant effects were seen with 30 µM myo-inositol (physiological) for 13C-palmitic-acid-lysophosphatidylcholines (1.26) and 13C-palmitic-acid-phosphatidylethanolamines (1.17). At 48 h, myo-inositol addition increased 13C-oleic-acid-lipids but decreased 13C-palmitic-acid and 13C-docosahexaenoic-acid lipids. Significant effects were seen with 30 µM myo-inositol for 13C-oleic-acid-phosphatidylcholines (1.25), 13C-oleic-acid-phosphatidylethanolamines (1.37) and 13C-oleic-acid-triacylglycerols (1.32) and with 100 µM myo-inositol for 13C-docosahexaenoic-acid-triacylglycerols (0.78). Lipids labeled with the same 13C-fatty-acid showed similar responses when tested at the same time-point, suggesting myo-inositol alters upstream processes such as fatty-acid uptake or activation. Myo-inositol supplementation may alter placental lipid physiology with unknown clinical consequences.

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ORCID for Keith Godfrey: orcid.org/0000-0002-4643-0618

ORCID for Rohan Lewis: orcid.org/0000-0003-4044-9104

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