title: Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes.
abstract: BACKGROUND
  Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling.
  
  
  RESULTS
  We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to "modify" the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals.
  
  
  CONCLUSIONS
  In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance, and dyslipidemia, but not with fasting glucose or blood pressure traits.
authors: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, Massachusetts, United States of America.|Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Jennifer E
authors: JE
authors: Ho
authors: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, Massachusetts, United States of America.|Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, United States of America.
authors: Martin G
authors: MG
authors: Larson
authors: Mount Auburn Hospital, Cambridge, Massachusetts, United States of America.
authors: Anahita
authors: A
authors: Ghorbani
authors: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, Massachusetts, United States of America.|Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Susan
authors: S
authors: Cheng
authors: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, Massachusetts, United States of America.
authors: Ming-Huei
authors: MH
authors: Chen
authors: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Michelle
authors: M
authors: Keyes
authors: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Renal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors: Eugene P
authors: EP
authors: Rhee
authors: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors: Clary B
authors: CB
authors: Clish
authors: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, Massachusetts, United States of America.|Division of Cardiology and Preventive Medicine, Department of Medicine, Boston University, Boston, Massachusetts, United States of America.
authors: Ramachandran S
authors: RS
authors: Vasan
authors: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors: Robert E
authors: RE
authors: Gerszten
authors: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors: Thomas J
authors: TJ
authors: Wang
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D050171:Dyslipidemias / Q000097:blood*; D005215:Fasting; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000097:blood*; D010641:Phenotype; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose