Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes

The Journal of Clinical Investigation
John O'SullivanRobert E Gerszten

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.

References

Feb 1, 1987·Archives of Biochemistry and Biophysics·T OgawaK Sasaoka
May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David E KleinerUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Jan 13, 2006·Therapeutic Drug Monitoring·Colin A SmithGary Siuzdak
May 10, 2008·Nature·Geoff Brumfiel
Jun 21, 2008·Journal of Gastroenterology and Hepatology·Elizabeth K SpeliotesCaroline S Fox
Dec 29, 2009·Nature Genetics·Thomas IlligKarsten Suhre
Dec 31, 2009·Bioinformatics·Ming-Huei Chen, Qiong Yang
Jul 24, 2010·Journal of the American Society for Mass Spectrometry·A Gareth Brenton, A Ruth Godfrey
Mar 23, 2011·Nature Medicine·Thomas J WangRobert E Gerszten
May 17, 2011·Nature Genetics·Karsten SuhreMatthias Nauck
Sep 3, 2011·Nature·Karsten SuhreChristian Gieger
Dec 14, 2011·Human Molecular Genetics·Taru TukiainenSamuli Ripatti
Jan 29, 2013·Journal of Clinical Lipidology·Piers R Blackett, Dharambir K Sanghera
Mar 8, 2013·PloS One·Miaoqing ShenOwen A Hoekenga
Jul 5, 2013·Cell Metabolism·Eugene P RheeRobert E Gerszten
Oct 9, 2014·Trends in Pharmacological Sciences·Roman N RodionovSteven R Lentz
May 9, 2015·World Journal of Gastroenterology : WJG·Andrea FerrignoMariapia Vairetti
Jun 10, 2015·JAMA : the Journal of the American Medical Association·Mary E Rinella
Sep 25, 2015·Nucleic Acids Research·Sunghwan KimStephen H Bryant
Jul 28, 2016·Nature Communications·Eugene P RheeRobert E Gerszten

❮ Previous
Next ❯

Citations

Jun 30, 2018·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Stephen T VernonGemma A Figtree
Aug 28, 2018·Diabetes, Obesity & Metabolism·Edward YuMiguel A Martínez-González
Nov 14, 2018·The Journal of Clinical Endocrinology and Metabolism·Marta Guasch-FerréJordi Salas-Salvadó
Jul 11, 2019·Molecular Nutrition & Food Research·Pablo Hernández-AlonsoJordi Salas-Salvadó
May 22, 2020·Circulation Research·Zsu-Zsu Chen, Robert E Gerszten
Jul 24, 2020·Cardiovascular Research·Matthias Barton, Carmine Cardillo
Sep 27, 2019·Environmental Health Perspectives·Dinesh Kumar Barupal, Oliver Fiehn
Sep 20, 2019·International Journal of Molecular Sciences·Natalia JarzebskaRoman N Rodionov
Jun 6, 2019·Frontiers in Nutrition·Gabriela PingetLaurence Macia
Aug 23, 2019·Physiological Reviews·David S Wishart
Apr 3, 2020·Cardiovascular Research·Yen Chin KoayJohn F O'Sullivan
Jul 15, 2020·American Journal of Physiology. Endocrinology and Metabolism·Jibran A WaliJohn F O'Sullivan
Aug 24, 2018·JCI Insight·Matthew L SteinhauserPouneh K Fazeli
Sep 11, 2019·The Journal of Clinical Endocrinology and Metabolism·Filip OttossonOlle Melander
Dec 21, 2018·Journal of the American Heart Association·Xia JiangChristopher Kabrhel
Oct 20, 2020·Circulation·Venkatesh L MurthyRavi V Shah
Oct 31, 2020·The Journal of Clinical Endocrinology and Metabolism·Lars LindJan Oscarsson
Oct 6, 2020·The Journal of Clinical Endocrinology and Metabolism·Yi GuoMin Xia
Jan 1, 2021·The Journal of Nutrition·Marta Guasch-FerréJordi Salas-Salvadó
Jan 20, 2021·Circulation. Heart Failure·Usman A TahirRobert E Gerszten
Dec 9, 2020·International Journal of Molecular Sciences·Małgorzata SzczukoMaciej Ziętek
Jan 15, 2021·The Journal of Clinical Investigation·Eriene-Heidi SidhomAnna Greka
Feb 17, 2021·JCI Insight·Debby NgoRobert E Gerszten
Feb 26, 2021·Molecular Nutrition & Food Research·Casey M RebholzJames G Wilson
Mar 21, 2021·The American Journal of Clinical Nutrition·Jean-Philippe Drouin-ChartierFrank B Hu
Apr 24, 2021·Journal of Hepatology·Taekyeong YooUNKNOWN Innovative Target Exploration of NAFLD (ITEN) consortium
Jul 31, 2021·Journal of the American College of Cardiology·Matthew NayorRavi V Shah

❮ Previous
Next ❯

Methods Mentioned

BETA
metabolomic profiling
metabolomic
gastric bypass
biopsy
column chromatography
PCR
metabolomics profiling

Software Mentioned

Progenesis QI
Sciex MultiQuant
SPSS
GraphPad Prism
Minimac
MACH
TraceFinder
GraphPad
SAS
METLIN

Related Concepts

Related Feeds

Biomarkers for Cardiovascular Risk Assessment

Sensitive and accurate biomarkers used in cardiovascular risk prediction can potentially be used to manage the risk of cardiovascular disease. Discover the latest research on Biomarkers for Cardiovascular Risk Assessment here. Discover the latest research on Biomarkers for Cardiovascular Risk Assessment here.

Biomarkers for Diabetes

This feed focuses on the latest research on biomarkers used for monitoring disease progression in diabetes.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
Keisuke OeToshiji Saibara
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology
Ryosuke Tateishi, Kazuhiko Koike
International Journal of Obesity : Journal of the International Association for the Study of Obesity
M MancoValerio Nobili
© 2022 Meta ULC. All rights reserved