Symmetric dimethylguanidino valeric acid, a novel single biomarker of hepatic steatosis

Roman N Rodionov; Natalia Jarzebska; Yen Chin Koay; Mengbo Li; Matthias Kuhn; Stefan R Bornstein; Jens Martens-Lobenhoffer; Mohammad Eslam; Fei Wen Chen; Elena Rubets; Alexander G Markov; Norbert Weiss; Andreas Birkenfeld; Peter Schwarz; Stefanie M Bode-Böger; Nikolaos Perakakis; John F O'Sullivan; Jacob George

doi:10.1016/j.isci.2024.111366

Symmetric dimethylguanidino valeric acid, a novel single biomarker of hepatic steatosis

iScience. 2024 Nov 13;27(12):111366. doi: 10.1016/j.isci.2024.111366. eCollection 2024 Dec 20.

Authors

Roman N Rodionov^{1

2}, Natalia Jarzebska^{1

3}, Yen Chin Koay^{4

5}, Mengbo Li^{6

7}, Matthias Kuhn⁸, Stefan R Bornstein^{1

9

10}, Jens Martens-Lobenhoffer¹¹, Mohammad Eslam¹², Fei Wen Chen¹³, Elena Rubets¹⁴, Alexander G Markov¹⁴, Norbert Weiss¹, Andreas Birkenfeld^{9

15

16}, Peter Schwarz^{1

9

11}, Stefanie M Bode-Böger¹², Nikolaos Perakakis^{1

9

11}, John F O'Sullivan^{1

4

5

17}, Jacob George¹²

Affiliations

¹ Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
² College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, SA 5042 Australia.
³ Department of Anaesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
⁴ Cardiometabolic Medicine, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
⁵ Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
⁶ Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
⁷ Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
⁸ Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁹ German Center for Diabetes Research (DZD e.V.), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
¹⁰ Department of Diabetes, School of Life Course Science and Medicine, King's College London, London, UK.
¹¹ Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany.
¹² Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
¹³ Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.
¹⁴ Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia.
¹⁵ Department of Internal Medicine IV, Department of Endocrinology, Diabetology and Nephrology, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany.
¹⁶ Germany and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls University of Tübingen, 72074 Tübingen, Germany.
¹⁷ Department of Cardiology, Royal Price Alfred Hospital, Sydney, NSW, Australia.

Abstract

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.

Keywords: Clinical finding; Health sciences; Physiological state.