Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry
Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry
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DOI：
10.1016/j.ymgme.2016.12.013
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发表时间：
2017-03-01
影响因子：
3.8
通讯作者：
Shimozawa, Nobuyuki
中科院分区：
文献类型：
--
作者：
Takashima, Shigeo;Toyoshi, Kayoko;Shimozawa, Nobuyuki
在过氧酶体疾病患者中，由于涉及过氧酶体功能的基因受损而发生代谢变化。为了诊断的目的，饱和的超长链脂肪酸(VLCFA)，如C24：0和06：0，植酸，普里斯坦酸和血浆原经常被测量为代谢标志。由于过氧酶体疾病的直接病理尚未完全阐明，我们试图探索过氧酶体疾病患者体内积累的脂肪酸种类。我们开发了一种方法来检测一系列与过氧酶体疾病有关的脂肪酸，如Zellweger综合征(Zellweger综合征)和X-连锁肾上腺脑白质营养不良(X-ALD)。为此，我们采用了带负电荷的电喷雾电离的超高效液-质联用(LC-MS)。采用酸水解法从患者和对照组的总脂肪中提取脂肪酸，并进行比较。与先前的结果一致，VLCFAs、植酸和伯斯坦酸的含量在两组之间存在差异。我们在ZS样品中发现了极长且高度多不饱和的VLC-PUFA(超VLC-PUFA)，如C44：12。此外，三个未知分子在对照样品中突出，但在ZS样品中几乎检测不到。LC-MS/MS分析确定这些化合物为1-烷基-sn-甘油3-磷酸盐，来源于含有脂肪醇的乙醚脂类，如C16：0、C18：0或C18：1。我们的方法提供了一种观察广泛的脂类衍生脂肪酸和相关分子的方法，以了解过氧酶体疾病涉及的代谢变化。因此，这项技术可用于确定代谢标记物和未来治疗的潜在临床靶点。(C)2017 Elsevier Inc.保留所有权利。
Metabolic changes occur in patients with peroxisomal diseases owing to impairments in the genes involved in peroxisome function. For diagnostic purposes, saturated very-long-chain fatty acids (VLCFAs) such as C24:0 and 06:0, phytanic acid, pristanic acid, and plasmalogens are often measured as metabolic hallmarks. As the direct pathology of peroxisomal disease is yet to be fully elucidated, we sought to explore the fatty acid species that accumulate in patients with peroxisomal diseases. We developed a method for detecting a range of fatty acids implicated in peroxisomal diseases such as Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD). To this end, we employed an ultra-performance liquid chromatography-mass spectrometry (LC-MS) coupled with negatively charged electrospray ionization. Fatty acids from patients and control subjects were extracted from total lipids by acid-hydrolysis and compared. In accordance with previous results, the amounts of VLCFAs, phytanic acid, and pristanic acid differed between the two groups. We identified extremely long and highly polyunsaturated VLCFAs (ultra-VLC-PUFAs) such as C44:12 in ZS samples. Moreover, three unknown molecules were prominent in control samples but scarcely detectable in ZS samples. LC-MS/MS analysis identified these as 1-alkyl-sn-glycerol 3-phosphates derived from ether lipids containing fatty alcohols such as C16:0, C18:0, or C18:1. Our method provides an approach to observing a wide range of lipid-derived fatty acids and related molecules in order to understand the metabolic changes involved in peroxisomal diseases. This technique can therefore be used in identifying metabolic markers and potential clinical targets for future treatment. (C) 2017 Elsevier Inc. All rights reserved.