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Well‐regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo‐inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope‐labelled 13C‐PA or 13C‐OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo‐inositol (0.3, 30, 60 μm). Forty‐seven 13C‐PA lipids and 37 13C‐OA lipids were measured by liquid chromatography–mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 13C‐OA lipids and nine 13C‐PA lipids, but decreased 13C‐OA phosphatidylethanolamine 38:5 and 13C‐PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13C‐OA acylcarnitine 18:1, and insulin increasing four 13C‐PA triacylglycerides. Most glucose, leptin and insulin‐induced alterations in lipids were attenuated by co‐incubation with myo‐inositol (30 or 60 μm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose‐induced increases in acylcarnitine were not attenuated by myo‐inositol and were even exaggerated in some instances. Myo‐inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo‐inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. Key points: Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13C‐lipids from 13C‐palmitic acid (PA) and 13C‐oleic acid (OA) in vitro compared with untreated controls from the same placenta.Co‐incubation with myo‐inositol attenuated most alterations induced by glucose, insulin or leptin in 13C‐lipids, but did not affect alterations in 13C‐acylcarnitines.Alterations induced by glucose and leptin in 13C‐PA triacylglycerides and 13C‐PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo‐inositol co‐incubation.Insulin differently affected 13C‐PA triacylglycerides and 13C‐PA phospholipids depending on fetal sex, with alterations also attenuated by myo‐inositol co‐incubation. [ABSTRACT FROM AUTHOR]

Transplacental docosahexaenoic-acid (DHA) supply for fetal development is regulated by placental DHA-lipid metabolism. Both maternal diabetes and obesity are linked to possible decreased fetal circulating DHA and increased placental DHA-lipids. Since myo-inositol is a promising intervention for gestational diabetes (GDM), we aimed to determine whether myo-inositol could rectify perturbations in placental DHA metabolism associated with maternal increasing glycemia and obesity and examine links with birthweight. Term placental villous explants from 17 women representing a range of BMIs and mid-gestational glycemia, were incubated with 13C-labeled-DHA for 48 h, in 0.3 µmol/L (control) or 60 µmol/L myo-inositol. Individual newly synthesized 13C-DHA-labeled lipid species were quantified by liquid-chromatography-mass-spectrometry. Compared with controls, incubation with myo-inositol decreased most 13C-DHA-lipids in placental explants from women with higher BMI or higher glycemia, but increased 13C-DHA-lipids with normal BMI or lower glycemia. Myo-inositol also increased 13C-DHA-labeled lipids in cases of lower birthweight centile, but induced decreases at higher centiles. Myo-inositol therefore lowered DHA-lipids in placenta with high basal placental DHA-lipid production (higher BMI and glycemia) but increased DHA-lipids where basal processing capacity is low. Myo-inositol thus moderates placental DHA metabolism towards a physiological mean which may in turn moderate birthweight. [ABSTRACT FROM AUTHOR]

Background: Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Methods: Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results: Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Conclusions: Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism. [ABSTRACT FROM AUTHOR]

We postulate that myo-inositol, a proposed intervention for gestational diabetes, affects transplacental lipid supply to the fetus. We investigate d 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 in dividual 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 acidphosphatidylethanolamines (1.17). At 48 h, myo-inositol addition increased 13C-oleic-acidlipids 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. [ABSTRACT FROM AUTHOR]