Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse.

chronic kidney disease diabetic nephropathy high-fat-diet leptin receptor-deficient mouse liver lungs metabolomics prediabetes and type 2 diabetes reduced kidney function

Journal

Metabolites
ISSN: 2218-1989
Titre abrégé: Metabolites
Pays: Switzerland
ID NLM: 101578790

Informations de publication

Date de publication:
03 Feb 2021
Historique:
received: 15 12 2020
revised: 27 01 2021
accepted: 29 01 2021
entrez: 6 2 2021
pubmed: 7 2 2021
medline: 7 2 2021
Statut: epublish

Résumé

Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.

Identifiants

pubmed: 33546276
pii: metabo11020089
doi: 10.3390/metabo11020089
pmc: PMC7913334
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Horizon 2020
ID : 19076 & 20679 iPDM-GO

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Auteurs

Jialing Huang (J)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.

Marcela Covic (M)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.

Cornelia Huth (C)

Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Martina Rommel (M)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Jonathan Adam (J)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Sven Zukunft (S)

Research Unit of Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Centre for Molecular Medicine, Institute for Vascular Signaling, Goethe University, 60323 Frankfurt am Main, Germany.

Cornelia Prehn (C)

Metabolomics and Proteomics Core Facility, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Li Wang (L)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Liaocheng People's Hospital-Department of Scientific Research, Shandong University Postdoctoral Work Station, Liaocheng 252000, China.

Jana Nano (J)

Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.

Markus F Scheerer (MF)

Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Bayer AG, Medical Affairs & Pharmacovigilance, 13353 Berlin, Germany.

Susanne Neschen (S)

Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Sanofi Aventis Deutschland GmbH, Industriepark Hoechst, 65929 Frankfurt am Main, Germany.

Gabi Kastenmüller (G)

Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Christian Gieger (C)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.

Michael Laxy (M)

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Jerzy Adamski (J)

Research Unit of Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85353 Freising, Germany.

Karsten Suhre (K)

Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar (WCMC-Q), Education City, Qatar Foundation, Doha P.O. Box 24144, Qatar.

Martin Hrabe de Angelis (MH)

German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85353 Freising, Germany.

Annette Peters (A)

Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.

Rui Wang-Sattler (R)

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.

Classifications MeSH