Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes.
<h4>Background</h4>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 sough...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0148361 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850212810279092224 |
|---|---|
| author | Jennifer E Ho Martin G Larson Anahita Ghorbani Susan Cheng Ming-Huei Chen Michelle Keyes Eugene P Rhee Clary B Clish Ramachandran S Vasan Robert E Gerszten Thomas J Wang |
| author_facet | Jennifer E Ho Martin G Larson Anahita Ghorbani Susan Cheng Ming-Huei Chen Michelle Keyes Eugene P Rhee Clary B Clish Ramachandran S Vasan Robert E Gerszten Thomas J Wang |
| author_sort | Jennifer E Ho |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-c0882e3e04374afa95283b93613cb055 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c0882e3e04374afa95283b93613cb0552025-08-20T02:09:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014836110.1371/journal.pone.0148361Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes.Jennifer E HoMartin G LarsonAnahita GhorbaniSusan ChengMing-Huei ChenMichelle KeyesEugene P RheeClary B ClishRamachandran S VasanRobert E GersztenThomas J Wang<h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0148361 |
| spellingShingle | Jennifer E Ho Martin G Larson Anahita Ghorbani Susan Cheng Ming-Huei Chen Michelle Keyes Eugene P Rhee Clary B Clish Ramachandran S Vasan Robert E Gerszten Thomas J Wang Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. PLoS ONE |
| title | Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. |
| title_full | Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. |
| title_fullStr | Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. |
| title_full_unstemmed | Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. |
| title_short | Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. |
| title_sort | metabolomic profiles of body mass index in the framingham heart study reveal distinct cardiometabolic phenotypes |
| url | https://doi.org/10.1371/journal.pone.0148361 |
| work_keys_str_mv | AT jennifereho metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT martinglarson metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT anahitaghorbani metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT susancheng metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT minghueichen metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT michellekeyes metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT eugeneprhee metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT clarybclish metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT ramachandransvasan metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT robertegerszten metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes AT thomasjwang metabolomicprofilesofbodymassindexintheframinghamheartstudyrevealdistinctcardiometabolicphenotypes |