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Celine Fernandez

Associate professor

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

Author

  • 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

Summary, in English

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.

Department/s

  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017-12-01

Language

English

Pages

4394-4402

Publication/Series

Journal of Clinical Investigation

Volume

127

Issue

12

Document type

Journal article

Publisher

Am Soc Clin Investig

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 0021-9738