Metabolic syndrome (MetS) is a multifactor condition predisposing for diabetes, cardiovascular diseases and other degenerative disorders. Although several diagnostic criteria have been established, none of them is specific and there is a call for better pathophysiological explanation of MetS and for the discovery of molecular biomarkers. Phenotype characterization at metabolome level might be useful for both purposes. To this end, our aim was to perform comparative untargeted metabolomics of urines from MetS patients and from the control group. The study participants included 52 diagnosticated and 50 healthy individuals from Leon city in central Mexico; 23 anthropometric and clinical parameters were measured and submitted to Principal Component Analysis (PCA). The obtained PCA model allowed us for selection of 11 MetS patients and 13 control subjects, correspondingly representative for each of the two groups (clearly separated in PCA). The first morning urines from these subjects were ambulatory collected and, after methanol extraction and acidification, were submitted to capillary liquid chromatography-high resolution mass spectrometry (LC-HRMS). The obtained data were analyzed on MetaboScape® platform (Bruker Daltonics). Specifically, t-test applied to LC-HRMS data revealed several ions presenting at least 3-fold higher intensities in MetS with respect to the control samples (p < 0.05). Data analysis and complementary experiments yielded the identification of the following metabolites: indole-3-acetic acid, indole-3-acetic acid-O-glucuronide, N-(indol-3-ylacetyl) glutamine, indole-3-carbaldehyde and hydroxyhexanoycarnitine. Additionally, indole-3-carboxylic acid was annotated with 2.13-fold higher abundance in MetS patients. To assess the contribution of individual metabolites in the difference between two groups of subjects, partial least square discriminant analysis was performed for LC-HRMS data and the obtained values of variable importance in projection (VIP), confirmed the association of six above mentioned compounds with MetS. Overall, this study provides direct evidence on the disturbed catabolism of tryptophan in metabolic syndrome.

中文翻译：

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液相色谱-质谱法非靶向代谢组学显示代谢综合征患者尿液中色氨酸吲哚代谢物水平升高

代谢综合征 (MetS) 是一种多因素疾病，易患糖尿病、心血管疾病和其他退行性疾病。虽然已经建立了几个诊断标准，但没有一个是具体的，因此需要更好的 MetS 病理生理学解释和分子生物标志物的发现。代谢组水平的表型表征可能对这两个目的都有用。为此，我们的目标是对来自 MetS 患者和对照组的尿液进行非靶向代谢组学的比较。研究参与者包括来自墨西哥中部莱昂市的 52 名确诊患者和 50 名健康人；测量了 23 个人体测量学和临床参数并提交给主成分分析 (PCA)。获得的 PCA 模型允许我们选择 11 名 MetS 患者和 13 名对照受试者，分别代表两组中的每一组（在 PCA 中明确分开）。这些受试者的第一次晨尿是动态收集的，在甲醇提取和酸化后，提交给毛细管液相色谱-高分辨质谱 (LC-HRMS)。在 MetaboScape® 平台 (Bruker Daltonics) 上分析获得的数据。具体而言，应用于 LC-HRMS 数据的 t 检验显示，相对于对照样品，几种离子在 MetS 中的强度至少高出 3 倍（p < 0.05）。数据分析和补充实验确定了以下代谢物：吲哚-3-乙酸、吲哚-3-乙酸-O-葡萄糖醛酸、N-（吲哚-3-基乙酰基）谷氨酰胺、吲哚-3-甲醛和羟基己酰基肉碱。此外，在 MetS 患者中，吲哚-3-羧酸的丰度高出 2.13 倍。为了评估个体代谢物对两组受试者差异的贡献，对 LC-HRMS 数据和获得的投影变量重要性 (VIP) 值进行了偏最小二乘判别分析，证实了上述六种化合物与大都会。总的来说，这项研究提供了代谢综合征中色氨酸分解代谢紊乱的直接证据。对 LC-HRMS 数据进行了偏最小二乘判别分析，获得的投影中可变重要性值 (VIP) 证实了上述六种化合物与 MetS 的关联。总的来说，这项研究提供了代谢综合征中色氨酸分解代谢紊乱的直接证据。对 LC-HRMS 数据进行了偏最小二乘判别分析，获得的投影中可变重要性值 (VIP) 证实了上述六种化合物与 MetS 的关联。总的来说，这项研究提供了代谢综合征中色氨酸分解代谢紊乱的直接证据。