Metabolism of 13C-labeled fatty acids in term human placental explants by liquid chromatography mass spectrometry

Abstract

Placental lipid transport and metabolism is poorly understood despite its importance for fetal development and life-long health. We aimed to explore fatty acid (FA) processing in human villous placental explants from seven uncomplicated term singleton pregnancies delivered by elective cesarean section. Explants were treated with stable-isotope labeled palmitic acid (13C-PA), oleic acid (13C-OA) or docosahexaenoic acid (13C-DHA) for 3, 24 or 48 hours. Stable isotope labeled lipids synthesised by placental explants from labelled FA were quantified, alongside endogenous unlabeled placental lipids, by liquid-chromatography mass-spectrometry. Labeled phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines were detected in explants, whilst labeled lysophosphatidylcholines were found in both explants and conditioned-media. 13C-PA was primarily directed into PC synthesis (74% of 13C-PA-labeled lipids), while 13C-OA was directed almost equally into PC and TAG synthesis (45% and 53%, respectively, of 13C-OA-labeled lipids). 13C-DHA was only detectable in TAGs. TAGs demonstrated the highest isotopic enrichment for all 13C-FAs with 13C-OA-TAGs comprising >50% of total OA-TAGs (unlabelled and labeled); consistent with TAGs being a labile and accessible reservoir for FA storage. Variations in lipid incorporation were correlated to maternal glycemia and BMI suggesting that this experimental model could be used to investigate the effect of maternal factors on placental lipid metabolism. We conclude that lipid metabolic partitioning of freshly-imported FAs into labile and less labile lipid reservoirs in placenta is FA-dependent. This process may partly mediate the physiological preferential transplacental transfer of particular FAs to the fetus, but may also be implicated in the fetoplacental pathophysiology of maternal metabolic dysfunction.

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