Lipidomic profiling identifies signatures of metabolic risk

Xiaoyan Yin, Christine M. Willinger, Joshua Keefe, Jun Liu, Antonio Fernandez-Ortiz, Borja Ibanez, Jose Penalvo, Aram Adourian, George Chen, Dolores Corella, Reinald Pamplona, Manuel Portero-Otin, Mariona Jove, Paul Courchesne, Cornelia M. van Duijn, Valentin Fuster, Jose M. Ordovas, Ayse Demirkan, Martin G. Larson, Daniel Levy*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    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.

    Original languageEnglish
    Article number102520
    Number of pages9
    JournalEBioMedicine
    Volume51
    DOIs
    Publication statusPublished - Jan-2020

    Keywords

    • Metabolic risk
    • Metabolic syndrome
    • Cardiovascular disease
    • Dysglycemia
    • Dyslipidemia
    • Biomarker
    • PLASMA SPHINGOLIPID METABOLISM
    • INDUCED INSULIN-RESISTANCE
    • CARDIOVASCULAR-DISEASE
    • ATHEROGENIC LIPOPROTEINS
    • DENSITY-LIPOPROTEIN
    • FASTING GLUCOSE
    • CERAMIDE
    • HEART
    • SPHINGOMYELIN
    • POPULATION

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