CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Laboratory of High-Resolution Mass Spectrometry Technologies, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China.
Theranostics. 2020 Jan 12;10(5):2029-2046. doi: 10.7150/thno.41106. eCollection 2020.
Metabolic syndrome (MTS) is a cluster of concurrent metabolic abnormal conditions. MTS and its component metabolic diseases are heterogeneous and closely related, making their relationships complicated, thus hindering precision treatment. : We collected seven groups of samples (group a: healthy individuals; group b: obesity; group c: MTS; group d: hyperglycemia, group e: hypertension, group f: hyperlipidemia; group g: type II diabetes, n=7 for each group). We examined the molecular characteristics of each sample by metabolomic, proteomic and peptidomic profiling analysis. The differential molecules (including metabolites, proteins and peptides) between each disease group and the healthy group were recognized by statistical analyses. Furthermore, a two-step clustering workflow which combines multi-omics and clinical information was used to redefine molecularly and clinically differential groups. Meanwhile, molecular, clinical, network and pathway based analyses were used to identify the group-specific biological features. : Both shared and disease-specific molecular profiles among the six types of diseases were identified. Meanwhile, the patients were stratified into three distinct groups which were different from original disease definitions but presented significant differences in glucose and lipid metabolism (Group 1: relatively favorable metabolic conditions; Group 2: severe dyslipidemia; Group 3: dysregulated insulin and glucose). Group specific biological signatures were also systematically described. The dyslipidemia group showed higher levels in multiple lipid metabolites like phosphatidylserine and phosphatidylcholine, and showed significant up-regulations in lipid and amino acid metabolism pathways. The glucose dysregulated group showed higher levels in many polypeptides from proteins contributing to immune response. The another group, with better glucose/lipid metabolism ability, showed higher levels in lipid regulating enzymes like the lecithin cholesterol acyltransferase and proteins involved in complement and coagulation cascades. : This multi-omics based study provides a general view of the complex relationships and an alternative classification for various metabolic diseases where the cross-talk or compensatory mechanism between the immune and metabolism systems plays a critical role.
代谢综合征（MTS）是一组并发的代谢异常情况。MTS 及其组成的代谢性疾病具有异质性且密切相关，使得它们的关系复杂，从而阻碍了精准治疗。我们收集了七组样本（a 组：健康个体；b 组：肥胖；c 组：MTS；d 组：高血糖；e 组：高血压；f 组：高血脂；g 组：2 型糖尿病，每组 7 例）。通过代谢组学、蛋白质组学和肽组学分析，我们检查了每个样本的分子特征。通过统计分析，识别出每个疾病组与健康组之间的差异分子（包括代谢物、蛋白质和肽）。此外，我们使用一种两步聚类工作流程，该流程结合了多组学和临床信息，用于重新定义分子和临床差异组。同时，使用基于分子、临床、网络和途径的分析方法来识别特定于组的生物学特征。在六种疾病中，我们鉴定出了共享和疾病特异性的分子特征。同时，将患者分为三个不同的组，与原始疾病定义不同，但在葡萄糖和脂质代谢方面存在显著差异（1 组：代谢条件相对较好；2 组：严重血脂异常；3 组：胰岛素和葡萄糖代谢失调）。还系统地描述了组特异性生物学特征。血脂异常组表现出多种脂质代谢物如磷脂酰丝氨酸和磷脂酰胆碱的水平升高，并且脂质和氨基酸代谢途径显著上调。葡萄糖失调组表现出许多来自参与免疫反应的蛋白质的多肽水平升高。另一个具有更好的葡萄糖/脂质代谢能力的组表现出更高水平的脂质调节酶，如卵磷脂胆固醇酰基转移酶，以及参与补体和凝血级联的蛋白质。基于多组学的研究提供了对各种代谢性疾病复杂关系的总体认识，并提供了一种替代分类方法，其中免疫和代谢系统之间的串扰或补偿机制起着关键作用。
