Serum metabolomics study of narcolepsy type 1 based on ultra-performance liquid chromatography–tandem mass spectrometry

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Amino Acids Pub Date : 2023-09-10 DOI:10.1007/s00726-023-03315-z

Qingqing Zhan, Lili Wang, Nan Liu, Yuqing Yuan, Liying Deng, Yongmin Ding, Fen Wang, Jian Zhou, Liang Xie

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Abstract

Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography–tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis.

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基于超高效液相色谱-串联质谱法的1型发作性睡病血清代谢组学研究。

嗜睡症是一种慢性且未被充分认识的睡眠障碍，其特征是白天过度嗜睡和猝倒。此外，1型嗜睡症（NT1）对个人的健康、社会和经济有严重的负面影响。目前，许多睡眠中心缺乏测量脑脊液中食欲素水平的方法。我们旨在通过超高效液相色谱-串联质谱法分析NT1患者代谢产物变化的特征。采用主成分分析（PCA）、正交偏最小二乘判别分析（OPLS-DA）、t检验和火山图构建发作性睡病异常代谢途径模型。我们确定了发作性睡病患者血清样本的分子变化，并根据OPLS负荷图分析，将其与对照组进行比较，包括脱氢表雄酮、肾上腺素、N-甲基-D-天冬氨酸和其他代谢物。九种代谢物在受试者工作曲线下产生一个区域 > 0.75.同时，7种异常代谢途径与差异代谢产物相关，如代谢途径；神经活性配体-受体相互作用；以及甘氨酸、丝氨酸和苏氨酸代谢。据我们所知，这是首次揭示NT1患者血清中特征性代谢产物变化的研究，用于选择潜在的血液生物标志物和阐明NT1的发病机制。

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来源期刊

Amino Acids 生物-生化与分子生物学

CiteScore

6.40

自引率

5.70%

发文量

审稿时长

2.2 months

期刊介绍： Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered. Fields of interest include: Biochemistry, food chemistry, nutrition, neurology, psychiatry, pharmacology, nephrology, gastroenterology, microbiology