BACKGROUND Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. METHODS We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. RESULTS Thirty-nine lipids were associated with obesity and eight with dysglycemia in the FHS. Of 32 lipids that were available for replication for obesity and six for dyslipidemia, 28 (88%) replicated for obesity and five (83%) for dysglycemia. Four lipids were associated with longitudinal changes in body mass index and four were associated with changes in fasting blood glucose in the FHS. CONCLUSIONS We identified and replicated several novel lipid biomarkers of key metabolic traits. The lipid moieties identified in this study are involved in biological pathways of metabolic risk and can be explored for prognostic and therapeutic utility.

中文翻译：

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脂质组学分析可识别代谢风险的特征。

背景技术代谢综合症（MetS），代谢危险因素的聚集，与心血管疾病的危险有关。我们试图确定脂质组的失调是否可能导致代谢危险因素。方法我们使用液相色谱-串联质谱法测量了Framingham心脏研究（FHS）的658名参与者中的154种循环脂质种类，并测试了与肥胖症，血糖异常和血脂异常的相关性。在三个独立的队列中寻求独立的外部验证。来自FHS的后续数据用于测试与代谢危险因素的纵向变化相关的脂质代谢产物。结果FHS中有39种脂质与肥胖有关，而8种与血糖异常有关。在肥胖症中可用于复制的32种脂质和血脂异常中可用于复制的6种脂质中，肥胖重复28次（88％），血糖异常重复5次（83％）。在FHS中，四种脂质与体重指数的纵向变化有关，而四种与空腹血糖的变化有关。结论我们鉴定并复制了关键代谢性状的几种新型脂质生物标志物。在这项研究中确定的脂质部分参与代谢风险的生物学途径，可以探索其预后和治疗用途。