Department of Physiology, School of Biology, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), University Clinical Hospital 'Virgen de la Arrixaca', University of Murcia, Murcia, Spain.
LMU - Ludwig-Maximilians-Universität Munich, Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Munich, Germany.
J Physiol. 2019 Oct;597(19):4959-4973. doi: 10.1113/JP278146. Epub 2019 Jul 24.
Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation.
We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: C-SA; palmitic acid: C-PA; oleic acid: C-OA) were orally administered at -4 h, -8 h and -12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20-25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11-12% h . No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal C-FA transfer was ∼1%. In conclusion, our approach using multiple C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.
母体肥胖会影响母胎脂肪酸(FA)的转运,从而改变胎盘的结构和功能。我们首次在人体和体内报告了使用稳定同位素在正常体重和正常脂血症肥胖孕妇中检测胎盘 FA 转移动力学的情况。通过在不同时间点给予与母体具有相似行为的不同示踪 FA,可以在仅收集每个受试者的一份胎盘和脐带样本的情况下,收集关于 FA 母胎转移的动力学信息。当考虑所有母体血浆脂质类时,计算模型与数据拟合良好,但仅基于非酯化 FA 时则不行。使用多种示踪 FA 给药并结合计算模型的新方法显示了胎盘示踪 FA 和预测的总 FA 积累的一致时间过程。
我们首次分析了在控制和肥胖(OB)孕妇中使用稳定同位素标记的体内 FA 的母胎动力学转移。在择期剖宫产前 4-4 小时、-8 小时和-12 小时,分别口服给予代谢相似的标记 FA(硬脂酸:C-SA;棕榈酸:C-PA;油酸:C-OA),以对 10 名体重指数(BMI)>30 的孕妇(OB)和 10 名 BMI 范围在 20-25 之间的孕妇(NW)进行研究。采集胎盘、静脉和动脉脐带血,获得广泛的 FA 富集度。应用了一种结合实验和计算模型分析的方法。胎盘 FA 合成率(FSR)为 11-12%/h。在 NW 和正常脂血症 OB 之间未观察到差异。用这种口服推注剂量方法无法估计脐带血中的 FA FSR。计算模型当包含所有母体血浆脂质类时拟合度较好,但仅基于非酯化 FA 分数建模则不行。估计的母子 C-FA 转移约为 1%。总之,我们使用多种 C-FA 示踪剂的方法允许我们估计胎盘/母体血浆中的 FSR,但不能估计胎儿/母体隔室中的 FSR。计算模型显示了胎盘 C-FA 转移的一致时间过程,并预测了实验过程中胎儿总 FA 的积累。我们得出结论,除了母体循环中的非酯化 FA 部分,母体血浆极低密度脂蛋白和其他脂蛋白是 FA 向胎儿转移的重要贡献者。