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足月低出生体重儿的广泛靶向血浆脂质组学分析:揭示特征及其对早期生长模式的影响

Widely targeted plasma lipidomic analysis of Term Low Birth Weight Infants: unraveling signatures and implications for early growth patterns.

作者信息

Liu Jing, Sun Qi, Tang Lijuan, Lv Di, Chen Yuanmei, Ye Fang, Liu Die, Liang Haixiao, Wang Chao, Zhang Qi

机构信息

Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China.

出版信息

J Pharm Biomed Anal. 2025 Jun 15;258:116732. doi: 10.1016/j.jpba.2025.116732. Epub 2025 Feb 6.

DOI:10.1016/j.jpba.2025.116732
PMID:39933396
Abstract

Low birth weight is recognized as a risk factor for adult metabolic and cardiovascular diseases. This study investigates whether term low birth weight (TLBW) neonates, who have been exposed to unfavorable settings, demonstrate compromised lipid metabolism. A widely targeted lipidomic analysis was conducted using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) on 59 plasma samples (28 TLBW and 31 term normal birth weight (TNBW) neonates. We conducted univariate and multivariate analyses to identify differential lipids. Spearman's correlation coefficient assessed the association between lipid content at birth and Z-scores for the subsequent physical growth of enrolled children. A total of 1523 lipids in 36 subcategories across 6 major categories were detected. 269 differential lipids were discerned, with 114 up-regulated and 155 down-regulated. In the TLBW group, we observed higher levels of sphingomyelins (including SM(d18:1/16:1), SM(d18:2/23:1), SM(d18:1/22:0), and SM(d18:2/24:1)), Hex3Cer(d18:1/16:0), as well as phosphatidylcholines (PC(O-14:0_20:4) and PC(O-16:0_20:4)), and cholesterol esters (CE (20:4)). In contrast, phosphatidylethanolamines (PE) such as PE (18:2_22:1), PE (18:1_22:1), and triglyceride (TG(10:0_16:2_18:2)) were lower. The KEGG enrichment analysis revealed a consistent alteration in both sphingolipid metabolism and steroid biosynthesis. Moreover, PC(O-16:0_20:4), Hex3Cer(d18:1/16:0), and CE(20:4) exhibited positive correlations with the Z-score of height-for-age at follow-up, while PE(O-18:1_24:4) and PS(20:2_22:4) showed negative correlations with the Z-score of weight-for-age. Our findings reveal novel lipidomic differences between TLBW and TNBW neonates. The observed lipid variations at birth, including sphingomyelins and glycerophospholipids, could affect subsequent growth. Further studies are needed to validate these findings in diverse populations, address confounding factors, and investigate underlying mechanisms.

摘要

低出生体重被认为是成人代谢和心血管疾病的一个风险因素。本研究调查了暴露于不利环境的足月低出生体重(TLBW)新生儿是否存在脂质代谢受损的情况。使用超高效液相色谱 - 串联质谱(UPLC - MS/MS)对59份血浆样本(28例TLBW新生儿和31例足月正常出生体重(TNBW)新生儿)进行了广泛靶向脂质组学分析。我们进行了单变量和多变量分析以识别差异脂质。Spearman相关系数评估了出生时的脂质含量与所纳入儿童随后身体生长的Z评分之间的关联。共检测到6大类36个亚类中的1523种脂质。辨别出269种差异脂质,其中114种上调,155种下调。在TLBW组中,我们观察到鞘磷脂(包括SM(d18:1/16:1)、SM(d18:2/23:1)、SM(d18:1/22:0)和SM(d18:2/24:1))、Hex3Cer(d18:1/16:0)以及磷脂酰胆碱(PC(O - 14:0_20:4)和PC(O - 16:0_20:4))和胆固醇酯(CE(20:4))水平较高。相比之下,磷脂酰乙醇胺(PE)如PE(18:2_22:1)、PE(18:1_22:1)和甘油三酯(TG(10:0_16:2_18:2))较低。KEGG富集分析显示鞘脂代谢和类固醇生物合成均存在一致的改变。此外,PC(O - 16:0_20:4)、Hex3Cer(d18:1/16:0)和CE(20:4)与随访时年龄别身高的Z评分呈正相关,而PE(O - 18:1_24:4)和PS(20:2_22:4)与年龄别体重的Z评分呈负相关。我们的研究结果揭示了TLBW和TNBW新生儿之间新的脂质组学差异。出生时观察到的脂质变化,包括鞘磷脂和甘油磷脂,可能会影响随后的生长。需要进一步研究以在不同人群中验证这些发现,解决混杂因素,并研究潜在机制。

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