Objective: To perform a comprehensive lipid profiling to evaluate potential lipid metabolic differences between patients with amyotrophic lateral sclerosis (ALS) and controls, and to provide a more profound understanding of the metabolic abnormalities in ALS. Methods: Twenty patients with ALS and 20 healthy controls were enrolled in a cross-sectional study. Untargeted lipidomics profiling in fasting serum samples were performed by optimized UPLC-MS platforms for broad lipidome coverage. Datasets were analyzed by univariate and a variety of multivariate procedures. Results: We provide the most comprehensive blood lipid profiling of ALS to date, with a total of 416 lipids measured. Univariate analysis showed that 28 individual lipid features and two lipid classes, triacylglycerides and oxidized fatty acids (FAs), were altered in patients with ALS, although none of these changes remained significant after multiple comparison adjustment. Most of these changes remained constant after removing from the analysis individuals treated with lipid-lowering drugs. The non-supervised principal component analysis did not identify any lipid clustering of patients with ALS and controls. Despite this, we performed a variety of linear and non-linear supervised multivariate models to select the most reliable features that discriminate the lipid profile of patients with ALS from controls. These were the monounsaturated FAs C24:1n-9 and C14:1, the triglyceride TG(51:4) and the sphingomyelin SM(36:2). Conclusions: Peripheral alterations of lipid metabolism are poorly defined in ALS, triacylglycerides and certain types of FAs could contribute to the different lipid profile of patients with ALS. These findings should be validated in an independent cohort.

中文翻译：

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肌萎缩性侧索硬化症的全面血清脂质组分析。

目的：进行全面的脂质分析，以评估肌萎缩性侧索硬化症（ALS）和对照患者之间潜在的脂质代谢差异，并提供对ALS代谢异常的更深刻理解。方法：20名ALS患者和20名健康对照组参加了一项横断面研究。通过优化的UPLC-MS平台对空腹血清样本中的非靶向脂质组学进行了分析，以覆盖广泛的脂质组。通过单变量和多种多元程序分析数据集。结果：我们提供了迄今为止最全面的ALS血脂分析，共测出416种血脂。单因素分析显示，ALS患者的28种个体脂质特征和两种脂质类别，三酰基甘油酯和氧化脂肪酸（FAs）发生了改变，尽管在进行多次比较调整后，这些变化均不显着。从分析中除去使用降脂药物治疗的个体后，大多数这些变化保持不变。非监督主成分分析未发现ALS和对照患者的任何脂质聚集。尽管如此，我们还是执行了各种线性和非线性有监督的多元模型，以选择最可靠的特征来区分ALS患者的脂质谱与对照。这些是单不饱和FA C24：1n-9和C14：1，甘油三酸酯TG（51：4）和鞘磷脂SM（36：2）。结论：ALS中脂代谢的周围改变定义不清，甘油三酸酯和某些类型的FAs可能会导致ALS患者不同的脂质分布。