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
Affiliations
Xiaoyan Yin
Framingham Heart Study, Framingham, MA, United States; Department of Mathematics and School of Public Health, Boston University, Boston, MA, United States
Christine M. Willinger
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
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
Department of Epidemiology, Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, Netherlands; Nuffield Department of Population Health, Oxford University, Oxford, UK
Antonio Fernández-Ortiz
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
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
Tufts University, Friedman School of Nutrition Science and Policy, Boston, MA, United States
Aram Adourian
BG Medicine, Inc., Waltham, MA, United States
George Chen
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
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
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain
Manuel Portero-Otin
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain
Mariona Jove
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain
Paul Courchesne
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
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
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
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
Department of Epidemiology, Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Genetics, University Medical Center Groningen, Groningen, Netherlands
Martin G. Larson
Framingham Heart Study, Framingham, MA, United States; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
Daniel Levy
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; Corresponding author: National Heart, Lung, and Blood Institute, Population Sciences Branch, 73 Mt. Wayte Ave, Suite 2, Framingham, MA, 01702, United States.
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: Metabolic risk, Metabolic syndrome, Cardiovascular disease, Dysglycemia, Dyslipidemia, Biomarker
