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

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 invest...

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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1152444/full
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author Robin Schürfeld
Benjamin Sandner
Annett Hoffmann
Annett Hoffmann
Nora Klöting
Ekaterine Baratashvili
Ekaterine Baratashvili
Marcin Nowicki
Sabine Paeschke
Joanna Kosacka
Susan Kralisch
Anette Bachmann
Armin Frille
Anja Dietel
Jens-Uwe Stolzenburg
Matthias Blüher
Matthias Blüher
Ming-Zhi Zhang
Ming-Zhi Zhang
Raymond C. Harris
Raymond C. Harris
Berend Isermann
Michael Stumvoll
Anke Tönjes
Thomas Ebert
author_facet Robin Schürfeld
Benjamin Sandner
Annett Hoffmann
Annett Hoffmann
Nora Klöting
Ekaterine Baratashvili
Ekaterine Baratashvili
Marcin Nowicki
Sabine Paeschke
Joanna Kosacka
Susan Kralisch
Anette Bachmann
Armin Frille
Anja Dietel
Jens-Uwe Stolzenburg
Matthias Blüher
Matthias Blüher
Ming-Zhi Zhang
Ming-Zhi Zhang
Raymond C. Harris
Raymond C. Harris
Berend Isermann
Michael Stumvoll
Anke Tönjes
Thomas Ebert
author_sort Robin Schürfeld
collection DOAJ
description 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.
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spelling doaj.art-a59255c85b8d475fb2073fe6e9442d052023-05-23T05:13:36ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-05-011410.3389/fendo.2023.11524441152444Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitorRobin Schürfeld0Benjamin Sandner1Annett Hoffmann2Annett Hoffmann3Nora Klöting4Ekaterine Baratashvili5Ekaterine Baratashvili6Marcin Nowicki7Sabine Paeschke8Joanna Kosacka9Susan Kralisch10Anette Bachmann11Armin Frille12Anja Dietel13Jens-Uwe Stolzenburg14Matthias Blüher15Matthias Blüher16Ming-Zhi Zhang17Ming-Zhi Zhang18Raymond C. Harris19Raymond C. Harris20Berend Isermann21Michael Stumvoll22Anke Tönjes23Thomas Ebert24Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyDepartment of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital Würzburg, Würzburg, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research of the Helmholtz Zentrum München at the University of Leipzig and University Hospital, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyDepartment of Cardiology, Angiology and Internal Intensive-Care Medicine, Klinikum St. Georg, Leipzig, GermanyInstitute of Anatomy, University of Leipzig, Leipzig, GermanyInstitute of Anatomy, University of Leipzig, Leipzig, GermanyDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyDepartment of Respiratory Medicine, University Hospital Leipzig, University of Leipzig, Leipzig, GermanyDepartment of Urology, University of Leipzig, Leipzig, GermanyDepartment of Urology, University of Leipzig, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research of the Helmholtz Zentrum München at the University of Leipzig and University Hospital, Leipzig, GermanyDivision of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States0Department of Medicine, Nashville Veterans Affairs Hospital, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States0Department of Medicine, Nashville Veterans Affairs Hospital, Vanderbilt University School of Medicine, Nashville, TN, United States1Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital Leipzig, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyObjectiveAcyl-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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1152444/fullAcyl-CoA-binding proteinadipokineschronic kidney diseasediabetic kidney diseasediazepam binding inhibitorhemodialysis
spellingShingle Robin Schürfeld
Benjamin Sandner
Annett Hoffmann
Annett Hoffmann
Nora Klöting
Ekaterine Baratashvili
Ekaterine Baratashvili
Marcin Nowicki
Sabine Paeschke
Joanna Kosacka
Susan Kralisch
Anette Bachmann
Armin Frille
Anja Dietel
Jens-Uwe Stolzenburg
Matthias Blüher
Matthias Blüher
Ming-Zhi Zhang
Ming-Zhi Zhang
Raymond C. Harris
Raymond C. Harris
Berend Isermann
Michael Stumvoll
Anke Tönjes
Thomas Ebert
Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor
Frontiers in Endocrinology
Acyl-CoA-binding protein
adipokines
chronic kidney disease
diabetic kidney disease
diazepam binding inhibitor
hemodialysis
title Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor
title_full Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor
title_fullStr Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor
title_full_unstemmed Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor
title_short Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor
title_sort renal function is a major predictor of circulating acyl coa binding protein diazepam binding inhibitor
topic Acyl-CoA-binding protein
adipokines
chronic kidney disease
diabetic kidney disease
diazepam binding inhibitor
hemodialysis
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1152444/full
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