Myo-inositol alters ¹³C-labeled fatty acid metabolism in human placental explants

We postulate that myo-inositol, a proposed intervention for gestational diabetes, affects transplacental lipid supply to the fetus. We investigated the effect of myoinositol 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.