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

Frontiers in Endocrinology

Endocrinology

Armin Frille¹  Anja Dietel²  Jens-Uwe Stolzenburg²  Joanna Kosacka³  Ming-Zhi Zhang⁴  Raymond C. Harris⁴  Nora Klöting⁵  Marcin Nowicki⁶  Sabine Paeschke⁶  Berend Isermann⁷  Michael Stumvoll⁸  Thomas Ebert⁸  Susan Kralisch⁸  Anke Tönjes⁸  Robin Schürfeld⁸  Anette Bachmann⁸  Benjamin Sandner⁸  Ekaterine Baratashvili⁹  Annett Hoffmann^1,10  Matthias Blüher^1,11 

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

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

DOI  :  10.3389/fendo.2023.1152444

 received in 2023-01-27, accepted in 2023-05-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveAcyl-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/methodsSerum 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.ResultsMedian [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.ConclusionsCirculating 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.

【 授权许可】

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