Shiao‐Yng Chan

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 13 C‐PA or 13 C‐OA for 48 h. Explants were treated with glucose (5, 10 m m ) or leptin (13 n m ) or insulin (150 n m ) in combination with myo‐inositol (0.3, 30, 60 μ m ). Forty‐seven 13 C‐PA lipids and 37 13 C‐OA lipids were measured by liquid chromatography–mass spectrometry (LCMS). Compared with controls (5 m m glucose), glucose (10 m m ) increased 19 13 C‐OA lipids and nine 13 C‐PA lipids, but decreased 13 C‐OA phosphatidylethanolamine 38:5 and 13 C‐PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13 C‐OA acylcarnitine 18:1, and insulin increasing four 13 C‐PA triacylglycerides. Most glucose, leptin and insulin‐induced alterations in lipids were attenuated by co‐incubation with myo‐inositol (30 or 60 μ m ), 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. image Key points Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13 C‐lipids from 13 C‐palmitic acid (PA) and 13 C‐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 13 C‐lipids, but did not affect alterations in 13 C‐acylcarnitines. Alterations induced by glucose and leptin in 13 C‐PA triacylglycerides and 13 C‐PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo‐inositol co‐incubation. Insulin differently affected 13 C‐PA triacylglycerides and 13 C‐PA phospholipids depending on fetal sex, with alterations also attenuated by myo‐inositol co‐incubation.