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脂质组学揭示了用于检测女孩中枢性性早熟的神经酰胺生物标志物。

Lipidomics reveals ceramide biomarkers for detecting central precocious puberty in girls.

机构信息

Undergraduate and Graduate Programs of Nutrition Science, College of Life Science, National Taiwan Normal University, Taipei, Taiwan; School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.

School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan.

出版信息

Obes Res Clin Pract. 2024 Jul-Aug;18(4):269-279. doi: 10.1016/j.orcp.2024.07.005. Epub 2024 Aug 10.

DOI:10.1016/j.orcp.2024.07.005
PMID:39127601
Abstract

BACKGROUND

Pubertal timing is modulated by complex interactions between the pituitary and gonadal sex steroid hormones. Evidence indicates that sphingolipids are involved in the biosynthesis of steroid hormones at multiple levels.

METHOD

This study recruited adolescent female patients from pubertal and pediatric endocrine clinics in Northern and Southern Taiwan from the Taiwan Puberty Longitudinal Study. A total of 112 plasma samples (22 healthy control, 29 peripheral precocious puberty (PPP), and 61 CPP samples) were collected. We extracted lipids from the plasma samples using the modified Folch method. The un-targeted ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed for the lipid analysis.

RESULTS

We identified sphingolipid-linked metabolites, including Cer(18:0/15:0), Cer(18:1/16:0), and Cer(18:1/26:0) as candidate biomarkers for distinguishing girls with CPP from the control group by using an excellent discrimination model (AUC = 0.964). Moreover, Cer(18:0/22:0) and Cer(d18:0/18:1) were identified as potential biomarkers of PPP, with an AUC value of 0.938. Furthermore, CerP(18:1/18:0) was identified as the sole candidate biomarker capable of differentiating CPP from PPP.

CONCLUSIONS

The biomarkers identified in this study can facilitate the accurate detection of CPP in girls, provide insights into lipid-linked pathophysiology, and present a novel method of monitoring the progression of this disorder.

摘要

背景

青春期启动是由垂体和性腺甾体激素之间复杂的相互作用所调节的。有证据表明,神经鞘脂类物质在甾体激素的生物合成的多个水平上参与其中。

方法

本研究从台湾青春期纵向研究中招募了来自北部和南部台湾青春期和儿科内分泌诊所的青春期女性患者。共收集了 112 份血浆样本(22 份健康对照、29 份外周性早熟(PPP)和 61 份 CPP 样本)。我们使用改良的 Folch 法从血浆样本中提取脂质。采用非靶向超高效液相色谱串联质谱(UPLC-MS/MS)进行脂质分析。

结果

我们确定了神经鞘脂类相关代谢物,包括 Cer(18:0/15:0)、Cer(18:1/16:0)和 Cer(18:1/26:0),可通过优秀的区分模型(AUC = 0.964)将 CPP 女孩与对照组区分开来。此外,Cer(18:0/22:0)和 Cer(d18:0/18:1)被鉴定为 PPP 的潜在生物标志物,AUC 值为 0.938。此外,CerP(18:1/18:0)被鉴定为唯一能够区分 CPP 与 PPP 的候选生物标志物。

结论

本研究中鉴定的生物标志物可有助于女孩 CPP 的准确检测,深入了解与脂质相关的病理生理学,并提供监测该疾病进展的新方法。

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