Lipidomic profiling identifies signatures of metabolic risk

Xiaoyan Yin, Christine M Willinger, Joshua Keefe, Jun Liu, Antonio Fernández-Ortiz, Borja Ibáñez, José Peñalvo, Aram Adourian, George Chen, Dolores Corella, Reinald Pamplona, Manuel Portero-Otin, Mariona Jove, Paul Courchesne, Cornelia M van Duijn, Valentín Fuster, José M Ordovás, Ayşe Demirkan, Martin G Larson, Daniel Levy, Xiaoyan Yin, Christine M Willinger, Joshua Keefe, Jun Liu, Antonio Fernández-Ortiz, Borja Ibáñez, José Peñalvo, Aram Adourian, George Chen, Dolores Corella, Reinald Pamplona, Manuel Portero-Otin, Mariona Jove, Paul Courchesne, Cornelia M van Duijn, Valentín Fuster, José M Ordovás, Ayşe Demirkan, Martin G Larson, Daniel Levy

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.

Keywords: Biomarker; Cardiovascular disease; Dysglycemia; Dyslipidemia; Metabolic risk; Metabolic syndrome.

Conflict of interest statement

Declaration of Competing Interest Dr. Adourian contributed to this project while affiliated with BG Medicine, Inc., a biomarker discovery company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2019. Published by Elsevier B.V.

Figures

Fig. 1
Fig. 1
Flow chart of experimental design.

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