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

O’Sullivan, John F.; Morningstar, Jordan E.; Yang, Qiong; Zheng, Baohui; Gao, Yan; Jeanfavre, Sarah; Scott, Justin; Fernandez, Celine LU ; Zheng, Hui and O’Connor, Sean, et al. (2017) In Journal of Clinical Investigation 127(12). p.4394-4402
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... (More)

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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Journal of Clinical Investigation
volume
127
issue
12
pages
9 pages
publisher
The Journal of Clinical Investigation
external identifiers
  • scopus:85037121679
  • wos:000417141100017
ISSN
0021-9738
DOI
10.1172/JCI95995
language
English
LU publication?
yes
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dad48282-a2f0-4e0b-a471-4d0f293c1b29
date added to LUP
2017-12-18 09:32:16
date last changed
2018-03-25 04:41:42
@article{dad48282-a2f0-4e0b-a471-4d0f293c1b29,
  abstract     = {<p>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.</p>},
  author       = {O’Sullivan, John F. and Morningstar, Jordan E. and Yang, Qiong and Zheng, Baohui and Gao, Yan and Jeanfavre, Sarah and Scott, Justin and Fernandez, Celine and Zheng, Hui and O’Connor, Sean and Cohen, Paul and Vasan, Ramachandran S. and Long, Michelle T. and Wilson, James G. and Melander, Olle and Wang, Thomas J. and Fox, Caroline and Peterson, Randall T. and Clish, Clary B. and Corey, Kathleen E. and Gerszten, Robert E.},
  issn         = {0021-9738},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {4394--4402},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes},
  url          = {http://dx.doi.org/10.1172/JCI95995},
  volume       = {127},
  year         = {2017},
}