Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes

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 sign...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one Jg. 11; H. 2; S. e0148361
Hauptverfasser: Ho, Jennifer E., Larson, Martin G., Ghorbani, Anahita, Cheng, Susan, Chen, Ming-Huei, Keyes, Michelle, Rhee, Eugene P., Clish, Clary B., Vasan, Ramachandran S., Gerszten, Robert E., Wang, Thomas J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 10.02.2016
Public Library of Science (PLoS)
Schlagworte:
Adipose tissue
Adult
Amino acids
Biology and Life Sciences
Blood
Blood Glucose - metabolism
Blood pressure
Body mass
Body Mass Index
Cardiovascular diseases
Chain branching
Citric acid
Cotinine
Diabetes
Dyslipidemia
Dyslipidemias - blood
Fasting
Female
Genetic aspects
Genetic crosses
Glucose
Health risk assessment
Heart
Humans
Hyperglycemia
Hypertension
Insulin
Insulin Resistance
Isoleucine
Ketoglutaric acid
Kynurenic acid
Leucine
Male
Medicine and Health Sciences
Metabolic Networks and Pathways
Metabolic pathways
Metabolites
Metabolome
Metabolomics
Myocardium - metabolism
Obesity
Obesity - blood
Offspring
Ornithine
Pathways
Phenotype
Phenylalanine
Profiling
Prospective Studies
Tricarboxylic acid cycle
Tryptophan
Tyrosine
Urea
Valine
United States
United States > US
Massachusetts
ISSN:1932-6203, 1932-6203
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. 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. 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ObjectType-Undefined-3
Competing Interests: Drs. Gerszten, Vasan, Larson, and Wang are named as co-inventors on a pending patent application relating to metabolite predictors of diabetes, entitled ‘Multiplexed Biomarkers of Insulin Resistance’, application number PCT/US2009/049831, publication number WO2010005982. No monetary benefit has been received from this application by any coauthors to date. There are no other declarations relevant to employment, consultancy, patents, products in development or modified products. Further, the authors’ would like to confirm that this does not alter their adherence to PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: JEH SC REG TJW. Performed the experiments: JEH SC EPR CBC RSV REG TJW. Analyzed the data: MGL AG MHC MK. Contributed reagents/materials/analysis tools: MGL EPR CBC REG TJW. Wrote the paper: JEH MGL AG SC MHC MK EPR CBC RSV REG TJW.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0148361