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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]

Complexes formed by the alpha1 N‐terminal peptide of alpha‐lactalbumin and oleic acid (alpha1‐oleate) interact with lipid bilayers. Plasma membrane perturbations trigger tumor cell death but normal differentiated cells are more resistant, and their plasma membranes are less strongly affected. This study examined membrane lipid composition as a determinant of tumor cell reactivity. Bladder cancer tissue showed a higher abundance of unsaturated lipids enriched in phosphatidylcholine, PC (36:4) and PC (38:4), and sphingomyelin, SM (36:1) than healthy bladder tissue, where saturated lipids predominated and the lipid extracts from bladder cancer tissue inhibited the tumoricidal effect of the complex more effectively than healthy tissue extracts. Furthermore, unsaturated PC in solution inhibited tumor cell death, and the complex interacted with giant unilamellar vesicles formed by PC, confirming the affinity of alpha1‐oleate for fluid membranes enriched in PC. Quartz Crystal Microbalance with dissipation monitoring (QCM‐D) detected a preference of the complex for the liquid‐disordered phase, suggesting that the insertion into PC‐based membranes and the resulting membrane perturbations are influenced by membrane lipid saturation. The results suggest that the membrane lipid composition is functionally important and that specific unsaturated membrane lipids may serve as "recognition motifs" for broad‐spectrum tumoricidal molecules such as alpha1‐oleate. [ABSTRACT FROM AUTHOR]