Lipidomic profiling identifies signatures of metabolic risk.

Adult Aged Animals Biomarkers Cross-Sectional Studies Disease Susceptibility Female Humans Lipid Metabolism Lipidomics / methods Lipids / blood Longitudinal Studies Male Metabolic Syndrome / blood Middle Aged Risk Assessment Risk Factors
Biomarker Cardiovascular disease Dysglycemia Dyslipidemia Metabolic risk Metabolic syndrome

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Jan 2020
Historique:
received: 13 06 2019
revised: 19 10 2019
accepted: 25 10 2019
pubmed: 27 12 2019
medline: 3 10 2020
entrez: 27 12 2019
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

DOI: 10.1016/j.ebiom.2019.10.046 PMID: 31877415 PMC: PMC6938899
pubmed: 31877415
pii: S2352-3964(19)30716-9
doi: 10.1016/j.ebiom.2019.10.046
pmc: PMC6938899
pii:
doi:

Substances chimiques

Biomarkers 0
Lipids 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102520

Subventions

Organisme : NHLBI NIH HHS
ID : N01HC25195
Pays : United States

Informations de copyright

Copyright © 2019. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

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.

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Auteurs

Xiaoyan Yin (X)

Framingham Heart Study, Framingham, MA, United States; Department of Mathematics and School of Public Health, Boston University, Boston, MA, United States.

Christine M Willinger (CM)

Framingham Heart Study, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Joshua Keefe (J)

Framingham Heart Study, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Jun Liu (J)

Department of Epidemiology, Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, Netherlands; Nuffield Department of Population Health, Oxford University, Oxford, UK.

Antonio Fernández-Ortiz (A)

Tufts University, Friedman School of Nutrition Science and Policy, Boston, MA, United States; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Department of Cardiology, Hospital Clinico San Carlos, Madrid, Spain; CIBERCV, Madrid, Spain.

Borja Ibáñez (B)

Tufts University, Friedman School of Nutrition Science and Policy, Boston, MA, United States; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; CIBERCV, Madrid, Spain; Department of Cardiology, IIS-Fundación Jiménez Díaz, Madrid Spain.

José Peñalvo (J)

Tufts University, Friedman School of Nutrition Science and Policy, Boston, MA, United States.

Aram Adourian (A)

BG Medicine, Inc., Waltham, MA, United States.

George Chen (G)

Framingham Heart Study, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Dolores Corella (D)

Department of Preventive Medicine and Public Health, Genetic and Molecular Epidemiology Unit, School of Medicine, University of Valencia, Blasco Ibañez, 15, 46010, Valencia, Spain; CIBER Obesity and Nutrition, Madrid, Spain.

Reinald Pamplona (R)

Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.

Manuel Portero-Otin (M)

Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.

Mariona Jove (M)

Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.

Paul Courchesne (P)

Framingham Heart Study, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Cornelia M van Duijn (CM)

Department of Epidemiology, Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, Netherlands; Nuffield Department of Population Health, Oxford University, Oxford, UK; Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.

Valentín Fuster (V)

Tufts University, Friedman School of Nutrition Science and Policy, Boston, MA, United States; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicina at Mount Sinai School, New York, USA.

José M Ordovás (JM)

Tufts University, Friedman School of Nutrition Science and Policy, Boston, MA, United States; Jean Mayer USDA-Human Nutrition Research on Aging, Tufts University, Boston, MA, United States.

Ayşe Demirkan (A)

Department of Epidemiology, Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Genetics, University Medical Center Groningen, Groningen, Netherlands.

Martin G Larson (MG)

Framingham Heart Study, Framingham, MA, United States; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.

Daniel Levy (D)

Framingham Heart Study, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States. Electronic address: levyd@nih.gov.

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