Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor

Robin Schürfeld; Benjamin Sandner; Annett Hoffmann; Nora Klöting; Ekaterine Baratashvili; Marcin Nowicki; Sabine Paeschke; Joanna Kosacka; Susan Kralisch; Anette Bachmann; Armin Frille; Anja Dietel; Jens-Uwe Stolzenburg; Matthias Blüher; Ming-Zhi Zhang; Raymond C Harris; Berend Isermann; Michael Stumvoll; Anke Tönjes; Thomas Ebert

doi:10.3389/fendo.2023.1152444

Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor

Front Endocrinol (Lausanne). 2023 May 23:14:1152444. doi: 10.3389/fendo.2023.1152444. eCollection 2023.

Authors

Robin Schürfeld¹, Benjamin Sandner¹, Annett Hoffmann^{1

2}, Nora Klöting³, Ekaterine Baratashvili^{1

4}, Marcin Nowicki⁵, Sabine Paeschke⁵, Joanna Kosacka⁶, Susan Kralisch¹, Anette Bachmann¹, Armin Frille⁷, Anja Dietel⁸, Jens-Uwe Stolzenburg⁸, Matthias Blüher^{1

3}, Ming-Zhi Zhang^{9

10}, Raymond C Harris^{9

10}, Berend Isermann¹¹, Michael Stumvoll¹, Anke Tönjes¹, Thomas Ebert¹

Affiliations

¹ Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
² Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
³ Helmholtz Institute for Metabolic, Obesity and Vascular Research of the Helmholtz Zentrum München at the University of Leipzig and University Hospital, Leipzig, Germany.
⁴ Department of Cardiology, Angiology and Internal Intensive-Care Medicine, Klinikum St. Georg, Leipzig, Germany.
⁵ Institute of Anatomy, University of Leipzig, Leipzig, Germany.
⁶ Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany.
⁷ Department of Respiratory Medicine, University Hospital Leipzig, University of Leipzig, Leipzig, Germany.
⁸ Department of Urology, University of Leipzig, Leipzig, Germany.
⁹ Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
¹⁰ Department of Medicine, Nashville Veterans Affairs Hospital, Vanderbilt University School of Medicine, Nashville, TN, United States.
¹¹ Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.

Abstract

Objective: Acyl-CoA-binding protein (ACBP)/diazepam-binding inhibitor has lately been described as an endocrine factor affecting food intake and lipid metabolism. ACBP is dysregulated in catabolic/malnutrition states like sepsis or systemic inflammation. However, regulation of ACBP has not been investigated in conditions with impaired kidney function, so far.

Design/methods: Serum ACBP concentrations were investigated by enzyme-linked immunosorbent assay i) in a cohort of 60 individuals with kidney failure (KF) on chronic haemodialysis and compared to 60 individuals with a preserved kidney function; and ii) in a human model of acute kidney dysfunction (AKD). In addition, mACBP mRNA expression was assessed in two CKD mouse models and in two distinct groups of non-CKD mice. Further, mRNA expression of mACBP was measured in vitro in isolated, differentiated mouse adipocytes - brown and white - after exposure to the uremic agent indoxyl sulfate.

Results: Median [interquartile range] serum ACBP was almost 20-fold increased in KF (514.0 [339.3] µg/l) compared to subjects without KF (26.1 [39.1] µg/l) (p<0.001). eGFR was the most important, inverse predictor of circulating ACBP in multivariate analysis (standardized β=-0.839; p<0.001). Furthermore, AKD increased ACBP concentrations almost 3-fold (p<0.001). Increased ACBP levels were not caused by augmented mACBP mRNA expression in different tissues of CKD mice in vivo or in indoxyl sulfate-treated adipocytes in vitro.

Conclusions: Circulating ACBP inversely associates with renal function, most likely through renal retention of the cytokine. Future studies need to investigate ACBP physiology in malnutrition-related disease states, such as CKD, and to adjust for markers of renal function.

Keywords: Acyl-CoA-binding protein; adipokines; chronic kidney disease; diabetic kidney disease; diazepam binding inhibitor; hemodialysis; type 2 diabetes mellitus.

Copyright © 2023 Schürfeld, Sandner, Hoffmann, Klöting, Baratashvili, Nowicki, Paeschke, Kosacka, Kralisch, Bachmann, Frille, Dietel, Stolzenburg, Blüher, Zhang, Harris, Isermann, Stumvoll, Tönjes and Ebert.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carrier Proteins / genetics
Diazepam / metabolism
Diazepam Binding Inhibitor*
Humans
Indican / metabolism
Kidney / metabolism
Malnutrition* / metabolism
Mice
RNA, Messenger / metabolism

Substances

Diazepam Binding Inhibitor
Indican
Carrier Proteins
Diazepam
RNA, Messenger

Grants and funding

This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) – through SFB 1052, project number 209933838, CRC 1052/3, subprojects C6 (AT), B1 (MB), B4 (NK), and A1 (MS). RS was supported by a travel grant for the Diabetes congress 2023 by the German diabetes Association (DDG). TE was supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet, Stockholm, Sweden, a Karolinska Institutet Research Foundation grant, the Stiftelsen Stig och Gunborg Westman, the Swedish Kidney Foundation (Njurfonden), and the German Diabetes Association (DDG). TE was further funded through the EFSD Mentorship Programme supported by AstraZeneca. This work was additionally supported by a grant of the Deutsche Diabetes Gesellschaft to MB and MN (DDG 934300-002), as well as to AH (“Projektpreis der AG Diabetes und Niere 2020”). MB received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, Pfizer and Sanofi. AF was supported by the postdoctoral fellowship “MetaRot program” from the Federal Ministry of Education and Research (BMBF), Germany (FKZ 01EO1501, IFB Adiposity Diseases), a research grant from the Mitteldeutsche Gesellschaft für Pneumologie (MDGP) e.V. (2018-MDGP-PA-002), a junior research grant from the Medical Faculty, University of Leipzig (934100-012), and the PETictCAC” project (ERAPerMed_324), which was funded with tax funds on the basis of the budget passed by the Saxon State Parliament (Germany) under the frame of ERA PerMed (Horizon 2020). All mentioned funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.