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Mirea, A.-M.* ; Toonen, E.J.M.* ; van den Munckhof, I.* ; Munsterman, I.D.* ; Tjwa, E.T.T.L.* ; Jaeger, M.* ; Oosting, M.* ; Schraa, K.* ; Rutten, J.H.W.* ; van der Graaf, M.* ; Riksen, N.P.* ; de Graaf, J.* ; Netea, M.G.* ; Tack, C.J.* ; Chavakis, T. ; Joosten, L.A.B.*

Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes.

Mol. Med. 25:16 (2019)
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Open Access Gold
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Introduction: Non-alcoholic fatty liver disease (NAFLD) is becoming a major health problem worldwide. Inflammation plays an important role in disease pathogenesis and recent studies have shown a potential role for the neutrophil serine proteases (NSPs) proteinase-3 (PR3) and neutrophil elastase (NE) in NAFLD as well as an imbalance between NSPs and their natural inhibitor alpha-1 antitrypsin (AAT). The aim of this study was to investigate whether PR3 and NE plasma concentrations are associated with NAFLD and/or type 2 diabetes.Methods: To explore this hypothesis we used several cohorts: a cohort of 271 obese individuals with liver steatosis, a cohort of 41 patients with biopsy-proven NAFLD, a cohort of 401 obese type 2 diabetes patients and a cohort of 205 lean healthy controls; and measured PR3 and NE plasma concentrations. In addition, we measured AAT plasma concentrations in order to investigate if the ratios between NSPs and their natural inhibitor were altered in NAFLD and type 2 diabetes when compared to healthy controls.Results: Our data shows an increase in PR3 and NE concentrations and a decrease in AAT concentrations in obese patients when compared to controls. Moreover, PR3 plasma concentrations are increased in patients with liver steatosis. Furthermore, PR3 and NE concentrations in the liver are associated with the advanced stages of NAFLD characterized by NASH and/or liver fibrosis. Additionally, PR3 and NE concentrations were up-regulated in patients with type 2 diabetes when compared to lean and obese controls.Conclusion: We conclude that circulating levels of NSPs associate with obesity-related metabolic disorders. Further research is needed to clearly establish the role of these proteases and investigate whether they could be used as non-invasive markers for NAFLD and/or type 2 diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Obesity ; Inflammation ; Nafld ; Type 2 Diabetes ; Neutrophil Serine Proteases ; Alpha-1 Antitrypsin; Inflammation; Fibrosis; Obesity
ISSN (print) / ISBN 1076-1551
e-ISSN 1435-8123
Quellenangaben Volume: 25, Issue: 1, Pages: , Article Number: 16 Supplement: ,
Publisher Feinstein Inst. for Medical Research
Publishing Place 233 Spring St, New York, Ny 10013 Usa
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)