Abstract

Non‐alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP, and LAP3, all of which are up‐regulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, plasma proteome profiling can identify potential biomarkers and drug targets in liver disease.

Details

Title
Plasma proteome profiling discovers novel proteins associated with non‐alcoholic fatty liver disease
Author
Niu, Lili 1 ; Geyer, Philipp E 1 ; Nicolai J Wewer Albrechtsen 2   VIAFID ORCID Logo  ; Gluud, Lise L 3 ; Santos, Alberto 4 ; Doll, Sophia 1 ; Treit, Peter V 5 ; Holst, Jens J 6   VIAFID ORCID Logo  ; Knop, Filip K 7 ; Vilsbøll, Tina 8 ; Junker, Anders 8 ; Sachs, Stephan 9 ; Stemmer, Kerstin 9 ; Müller, Timo D 9 ; Tschöp, Matthias H 9 ; Hofmann, Susanna M 10 ; Mann, Matthias 1   VIAFID ORCID Logo 

1  Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany 
2  Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 
3  Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark 
4  Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark 
5  Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany 
6  Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark 
7  Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark 
8  Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark 
9  Helmholtz Diabetes Center at Helmholtz Centre Munich & Division of Metabolic Diseases, Institute for Diabetes and Obesity, Technische Universität München, Munich, Germany 
10  Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Medizinische Klinik und Poliklinik IV, Klinikum der LMU, München, Germany 
Section
Articles
Publication year
2019
Publication date
Mar 2019
Publisher
EMBO Press
e-ISSN
17444292
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.15252/msb.20188793
ProQuest document ID
2331412191
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.