Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy.
Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy.
复制标题
DOI：
10.1371/journal.pone.0145794
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Entringer S
中科院分区：
文献类型：
--
作者：
Lindsay KL;Hellmuth C;Uhl O;Buss C;Wadhwa PD;Koletzko B;Entringer S
怀孕的特点是代谢过程的复杂性，可能会影响胎儿发育，并最终影响婴儿的健康结果。然而，我们对母体和胎儿在这一关键生命阶段的全身代谢的理解仍然不完整。本研究的目的是利用代谢组学分析非糖尿病健康孕妇队列中空腹母体代谢物的纵向模式，以促进我们对整个妊娠期蛋白质和脂质浓度变化的理解，以及它们代谢的生化途径，并描述不同种族之间母体代谢物的变化。在160名孕妇中，氨基酸，三羧酸（TCA）循环中间体，酮体和非酯化脂肪酸的液相色谱-质谱联用检测，而极性脂质通过流动注射质谱检测。母体血浆中几种必需和非必需氨基酸、长链多不饱和脂肪酸、游离肉毒碱、乙酰肉毒碱、磷脂酰胆碱和鞘磷脂的浓度在整个妊娠期间显著降低。随着妊娠的进展，几种TCA中间体的浓度以及酮体β-羟基丁酸酯的浓度增加。特定酰基肉毒碱的比例作为代谢途径的指标，表明β-氧化率降低，肉毒碱棕榈酰转移酶-1酶活性增加，妊娠期提前。氨基酸浓度降低可能反映了胎盘摄取和组织生物合成。在妊娠后期的分解代谢阶段，血浆非酯化脂肪酸未出现任何增加，这是意料之外的，可能反映了胎盘脂肪酸的摄取和胎儿组织生长的利用增强。虽然看起来通过TCA循环的能量产生随着妊娠进展而增加，但游离肉碱和乙酰肉碱的减少模式以及肉碱棕榈酰转移酶-1速率和β-羟基丁酸水平的增加表明伴随着生酮的上调，以确保禁食状态下足够的能量供应。西班牙裔和非西班牙裔妇女之间的代谢谱的几个差异表明产前代谢的表型变异，这应该在未来的研究中考虑。
Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies.