Lipidomic profiling identifies signatures of metabolic risk

Authors: VIN, XIAOYAN - Boston University; WILLINGER, CHRISTINE - National Institutes Of Health (NIH); KEEFE, JOSHUA - National Institutes Of Health (NIH); LIU, JUN - Erasmus Medical Center; FERNANDEZ-ORTIZ, ANTONIO - Tufts University; IBANEZ, BORJA - Tufts University; PENALVO, JOSE - Tufts University; ADOURIAN, ARAM - Bg Medicine; CHEN, GEORGE - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH); CORELLA, DOLORES - University Of Valencia; PAMPLONA, REINALD - Universitat De Lleida; PORTERO-OTIN, MANUEL - Universitat De Lleida; JOVE, MARIONA - Universitat De Lleida; COURCHESNE, PAUL - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH); VAN DUIJN, CORNELIA - Erasmus Medical Center; FUSTER, VALENTIN - Tufts University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DEMIRKAN, AYSE - Erasmus Medical Center; LARSON, MARTIN - Boston University; LEVY, DANIEL - National Institutes Of Health (NIH)

Submitted to: EBioMedicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2019
Publication Date: 12/15/2019
Citation: Vin, X., Willinger, C.M., Keefe, J., Liu, J., Fernandez-Ortiz, A., Ibanez, B., Penalvo, J., Adourian, A., Chen, G., Corella, D., Pamplona, R., Portero-Otin, M., Jove, P., Courchesne, P., Van Duijn, C.M., Fuster, V., Ordovas, J.M., Demirkan, A., Larson, M.G., Levy, D. 2019. Lipidomic profiling identifies signatures of metabolic risk. EBioMedicine. 51:102520. https://doi.org/10.1016/j.ebiom.2019.10.046.
DOI: https://doi.org/10.1016/j.ebiom.2019.10.046

Interpretive Summary: Metabolic syndrome (MetS), a clustering of metabolic risk factors, is associated with cardiovascular disease risk. Investigators at the HNRCA in Boston, in collaboration with other researchers in the US and Europe, used an advanced technology, known as lipidomics, to determine if blood lipids may contribute to metabolic risk factors. This investigation was carried out on participants from the Framingham Heart Study (FHS). The results were validated in three other populations. The results revealed fifty blood lipids associated with metabolic risk factors present in MetS. These lipids could be explored for prognostic and therapeutic utility.

Technical 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.