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John F. O’Sullivan, … , Kathleen E. Corey, Robert E. Gerszten
Published October 30, 2017
Citation Information: J Clin Invest. 2017;127(12):4394-4402. https://doi.org/10.1172/JCI95995.
Citation Information: J Clin Invest. 2017;127(12):4394-4402. https://doi.org/10.1172/JCI95995.
Abstract
Unbiased, “nontargeted” metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack of successful applications to human disease. By integrating nontargeted metabolomics, genetics, and detailed human phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent biomarker of CT-defined nonalcoholic fatty liver disease (NAFLD) in the offspring cohort of the Framingham Heart Study (FHS) participants. We verified the relationship between DMGV and early hepatic pathology. Specifically, plasma DMGV levels were correlated with biopsy-proven nonalcoholic steatohepatitis (NASH) in a hospital cohort of individuals undergoing gastric bypass surgery, and DMGV levels fell in parallel with improvements in post-procedure cardiometabolic parameters. Further, baseline DMGV levels independently predicted future diabetes up to 12 years before disease onset in 3 distinct human cohorts. Finally, we provide all metabolite peak data consisting of known and unidentified peaks, genetics, and key metabolic parameters as a publicly available resource for investigations in cardiometabolic diseases.
Authors
John F. O’Sullivan, Jordan E. Morningstar, Qiong Yang, Baohui Zheng, Yan Gao, Sarah Jeanfavre, Justin Scott, Celine Fernandez, Hui Zheng, Sean O’Connor, Paul Cohen, Ramachandran S. Vasan, Michelle T. Long, James G. Wilson, Olle Melander, Thomas J. Wang, Caroline Fox, Randall T. Peterson, Clary B. Clish, Kathleen E. Corey, Robert E. Gerszten
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Pharmacometabolomics of Bronchodilator Response in Asthma and the Role of Age-Metabolite Interactions
RS Kelly, JE Sordillo, SM Lutz, L Avila, M Soto-Quiros, JC Celedón, MJ McGeachie, A Dahlin, K Tantisira, M Huang, CB Clish, ST Weiss, J Lasky-Su, AC Wu |
Metabolites | 2019 |
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Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction
G Pinget, J Tan, B Janac, NO Kaakoush, AS Angelatos, J O'Sullivan, YC Koay, F Sierro, J Davis, SK Divakarla, D Khanal, RJ Moore, D Stanley, W Chrzanowski, L Macia |
Frontiers in Nutrition | 2019 |
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Plasma Metabolites Associated with Coffee Consumption: A Metabolomic Approach within the PREDIMED Study
C Papandreou, P Hernández-Alonso, M Bulló, M Ruiz-Canela, E Yu, M Guasch-Ferré, E Toledo, C Dennis, A Deik, C Clish, C Razquin, D Corella, R Estruch, E Ros, M Fitó, F Arós, M Fiol, J Lapetra, C Ruano, L Liang, MA Martínez-González, FB Hu, J Salas-Salvadó |
Nutrients | 2019 |
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Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control
SM Solon-Biet, VC Cogger, T Pulpitel, D Wahl, X Clark, EE Bagley, GC Gregoriou, AM Senior, QP Wang, AE Brandon, R Perks, J OSullivan, YC Koay, K Bell-Anderson, M Kebede, B Yau, C Atkinson, G Svineng, T Dodgson, JA Wali, MD Piper, P Juricic, L Partridge, AJ Rose, D Raubenheimer, GJ Cooney, DG Couteur, SJ Simpson |
2019 | |
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Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise
JM Robbins, M Herzig, J Morningstar, MA Sarzynski, DE Cruz, TJ Wang, Y Gao, JG Wilson, C Bouchard, T Rankinen, RE Gerszten |
JAMA Cardiology | 2019 |
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Plasma Metabolites Associated with Frequent Red Wine Consumption: A Metabolomics Approach within the PREDIMED Study
P HernándezAlonso, C Papandreou, M Bulló, M RuizCanela, C Dennis, A Deik, DD Wang, M GuaschFerré, E Yu, E Toledo, C Razquin, D Corella, R Estruch, E Ros, M Fitó, F Arós, M Fiol, L SerraMajem, L Liang, CB Clish, MA MartínezGonzález, FB Hu, J SalasSalvadó |
Molecular Nutrition & Food Research | 2019 |
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Purine Metabolites and Carnitine Biosynthesis Intermediates Are Biomarkers for Incident Type 2 Diabetes
F Ottosson, E Smith, W Gallo, C Fernandez, O Melander |
The Journal of clinical endocrinology and metabolism | 2019 |
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The Second Life of Methylarginines as Cardiovascular Targets
N Jarzebska, AA Mangoni, J Martens-Lobenhoffer, SM Bode-Böger, RN Rodionov |
International journal of molecular sciences | 2019 |
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Dimethylguanidino Valerate: A Lifestyle‐Related Metabolite Associated With Future Coronary Artery Disease and Cardiovascular Mortality
F Ottosson, U Ericson, P Almgren, E Smith, L Brunkwall, S Hellstrand, PM Nilsson, M OrhoMelander, C Fernandez, O Melander |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2019 |
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Generating the Blood Exposome Database Using a Comprehensive Text Mining and Database Fusion Approach
DK Barupal, O Fiehn |
Environmental Health Perspectives | 2019 |
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Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood
Y Ji, RE Azuine, Y Zhang, W Hou, X Hong, G Wang, A Riley, C Pearson, B Zuckerman, X Wang |
JAMA PSYCHIAT | 2019 |
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Circulating Lysophosphatidylcholines, Phosphatidylcholines, Ceramides, and Sphingomyelins and Ovarian Cancer Risk: A 23-Year Prospective Study
OA Zeleznik, CB Clish, P Kraft, J Avila-Pacheco, AH Eliassen, SS Tworoger |
JNCI Journal of the National Cancer Institute | 2019 |
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The circulating metabolome of human starvation
Matthew Steinhauser, Benjamin Olenchock, John O'Keefe, Mingyue Lun, Kerry Pierce, Hang Lee, Lorena Pantano, Anne Klibanski, Gerald I. Shulman, Clary Clish, Pouneh Fazeli |
JCI Insight | 2018 |
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Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial
M Ruiz-Canela, M Guasch-Ferré, E Toledo, CB Clish, C Razquin, L Liang, DD Wang, D Corella, R Estruch, Á Hernáez, E Yu, E Gómez-Gracia, Y Zheng, F Arós, D Romaguera, C Dennis, E Ros, J Lapetra, L Serra-Majem, C Papandreou, O Portoles, M Fitó, J Salas-Salvadó, FB Hu, MA Martínez-González |
Diabetologia | 2018 |
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Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study
E Yu, C Papandreou, M Ruiz-Canela, M Guasch-Ferre, CB Clish, C Dennis, L Liang, D Corella, M Fitó, C Razquin, J Lapetra, R Estruch, E Ros, M Cofán, F Arós, E Toledo, L Serra-Majem, JV Sorlí, FB Hu, MA Martinez-Gonzalez, J Salas-Salvado |
Clinical chemistry | 2018 |
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Study of the Serum Metabolomic Profile in Nonalcoholic Fatty Liver Disease: Research and Clinical Perspectives
S Gitto, F Schepis, P Andreone, E Villa |
Metabolites | 2018 |
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Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial
E Yu, M Ruiz-Canela, C Razquin, M Guasch-Ferré, E Toledo, DD Wang, C Papandreou, C Dennis, C Clish, L Liang, M Bullo, D Corella, M Fitó, M Gutiérrez-Bedmar, J Lapetra, R Estruch, E Ros, M Cofán, F Arós, D Romaguera, L Serra-Majem, JV Sorlí, J Salas-Salvadó, FB Hu, MA Martínez-González |
Diabetes, obesity & metabolism | 2018 |
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Metabolites Associated With the Risk of Incident Venous Thromboembolism: A Metabolomic Analysis
X Jiang, OA Zeleznik, S Lindström, J LaskySu, K Hagan, CB Clish, AH Eliassen, P Kraft, C Kabrhel |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2018 |
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Plasma Acylcarnitines and Risk of Type 2 Diabetes in a Mediterranean Population at High Cardiovascular Risk
M Guasch-Ferré, M Ruiz-Canela, J Li, Y Zheng, M Bulló, DD Wang, E Toledo, C Clish, D Corella, R Estruch, E Ros, M Fitó, F Arós, M Fiol, J Lapetra, L Serra-Majem, L Liang, C Papandreou, C Dennis, MA Martínez-González, FB Hu, J Salas-Salvadó |
The Journal of clinical endocrinology and metabolism | 2018 |
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