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

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. CoreyRobert E. Gerszten

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4394-4402
Number of pages9
JournalJournal of Clinical Investigation
Volume127
Issue number12
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    O’Sullivan, J. F., Morningstar, J. E., Yang, Q., Zheng, B., Gao, Y., Jeanfavre, S., Scott, J., Fernandez, C., Zheng, H., O’Connor, S., Cohen, P., Vasan, R. S., Long, M. T., Wilson, J. G., Melander, O., Wang, T. J., Fox, C., Peterson, R. T., Clish, C. B., ... Gerszten, R. E. (2017). Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes. Journal of Clinical Investigation, 127(12), 4394-4402. https://doi.org/10.1172/JCI95995