TY - JOUR
T1 - Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes
AU - O’Sullivan, John F.
AU - Morningstar, Jordan E.
AU - Yang, Qiong
AU - Zheng, Baohui
AU - Gao, Yan
AU - Jeanfavre, Sarah
AU - Scott, Justin
AU - Fernandez, Celine
AU - Zheng, Hui
AU - O’Connor, Sean
AU - Cohen, Paul
AU - Vasan, Ramachandran S.
AU - Long, Michelle T.
AU - Wilson, James G.
AU - Melander, Olle
AU - Wang, Thomas J.
AU - Fox, Caroline
AU - Peterson, Randall T.
AU - Clish, Clary B.
AU - Corey, Kathleen E.
AU - Gerszten, Robert E.
N1 - Funding Information:
We thank Carolin Lerchenmuller for her help with translation of the protocol for synthesis of DMGV from the original publication in German. This study was supported by NIH grants K23DK99422 (to KC) and R01HL098280, U01DK048489, R01DK081572, U24DK112340 and DK 108159 (to REG).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI95995
DO - 10.1172/JCI95995
M3 - Article
C2 - 29083323
AN - SCOPUS:85037121679
SN - 0021-9738
VL - 127
SP - 4394
EP - 4402
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -