Symmetric dimethylguanidino valeric acid, a novel single biomarker of hepatic steatosis
There is an unmet need for a biomarker of liver fat. We identified dimethylguanidino valeric acid (DMGV) as a circulating biomarker of liver fat. Here, we assess its two isoforms-symmetric (SDGV) and asymmetric (ADGV)-as biomarkers of steatosis. We determined plasma ADGV, SDGV, related metabolites, alanine aminotransferase (ALT), and the fatty liver index (FLI) in two cohorts and compared their diagnostic performance for liver fat detection. SDGV was the strongest predictor of moderate to severe steatosis. Changes in SDGV correlated with changes in liver fat % in a prospective cohort. In a murine model of fatty liver disease, protein levels and activity of alanine:glyoxylate aminotransferase 2 (AGXT2), which produces SDGV, were increased and coincided with elevation of SDGV concentrations. SDGV is a biomarker of liver fat and its increase in hepatic steatosis results from the upregulation of AGXT2 activity.
Authors
- John O’Sullivan (ORCID: https://orcid.org/0000-0001-8016-5128)
- Yen Chin Koay (ORCID: https://orcid.org/0000-0002-6704-5495)
- Stefan R. Bornstein (ORCID: https://orcid.org/0000-0002-5211-2536)
- Norbert Weiss (ORCID: https://orcid.org/0000-0002-0040-1109)
- Jacob George (ORCID: https://orcid.org/0000-0002-8421-5476)
- Andreas L. Birkenfeld (ORCID: https://orcid.org/0000-0003-1407-9023)
- Mengbo Li (ORCID: https://orcid.org/0000-0002-9666-5810)
- Nikolaos Perakakis (ORCID: https://orcid.org/0000-0002-2319-6603)
- Matthias Kühn (ORCID: https://orcid.org/0000-0003-2868-5155)
- Roman N. Rodionov (ORCID: https://orcid.org/0000-0002-7470-7776)
- Alexander G. Markov (ORCID: https://orcid.org/0000-0002-2867-044X)
- Natalia Jarzebska (ORCID: https://orcid.org/0000-0002-1275-2942)
- Peter Schwarz (ORCID: https://orcid.org/0000-0003-4066-0102)
- Stefanie M. Bode‐Böger (ORCID: https://orcid.org/0000-0002-5132-6591)
- Mohammed Eslam (ORCID: https://orcid.org/0000-0002-4315-4144)
- Elena Rubets
- Jens Martens‐Lobenhoffer (ORCID: https://orcid.org/0000-0002-3829-7992)
- Fei Chen (ORCID: https://orcid.org/0000-0002-7251-5287)
Institutions
- The University of Sydney (AU)
- The University of Melbourne (AU)
- Flinders University (AU)
- St Petersburg University (RU)
- King's College London (GB)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Royal Prince Alfred Hospital (AU)
- Flinders Medical Centre (AU)
- Westmead Hospital (AU)
- Westmead Institute (AU)
- Westmead Institute for Medical Research (AU)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- University Hospital Carl Gustav Carus (DE)
- Paul Langerhans Institute Dresden (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technische Universität Dresden (DE)
- University of Tübingen (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- iScience
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1016/j.isci.2024.111366
- Citations
- 1
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- National Heart Foundation of Australia
- Cancer Institute NSW
- Bundesministerium für Bildung und Forschung
- Medical Research Council
- National Health and Medical Research Council