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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • John F. O’Sullivan
  • Jordan E. Morningstar
  • Qiong Yang
  • Baohui Zheng
  • Yan Gao
  • Sarah Jeanfavre
  • Justin Scott
  • Hui Zheng
  • Sean O’Connor
  • Paul Cohen
  • Ramachandran S. Vasan
  • Michelle T. Long
  • James G. Wilson
  • Thomas J. Wang
  • Caroline Fox
  • Randall T. Peterson
  • Clary B. Clish
  • Kathleen E. Corey
  • Robert E. Gerszten
Enheter & grupper
Externa organisationer
  • Massachusetts General Hospital
  • University of Sydney
  • Harvard Medical School
  • Boston University
  • University of Mississippi Medical Center
  • Broad Institute
  • Rockefeller University
  • Skåne University Hospital
  • Vanderbilt University
  • National Heart Lung and Blood Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
Originalspråkengelska
Sidor (från-till)4394-4402
Antal sidor9
TidskriftJournal of Clinical Investigation
Volym127
Utgivningsnummer12
StatusPublished - 2017 dec 1
PublikationskategoriForskning
Peer review utfördJa