Dipeptidylpeptidase (DPP)-4 inhibitor therapy increases circulating levels of anti-inflammatory soluble frizzle receptor protein (sFRP)-5 which is decreased in severe COVID-19 disease.

Autor: Brandes J; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., Zobel I; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., Rohmann N; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., Schlicht K; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., Geisler C; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., Hartmann K; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., Türk K; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany., von Schönfels W; Department of General and Abdominal Surgery, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany., Beckmann J; Department of General and Abdominal Surgery, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany., Tran F; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany., Laudes M; Institute of Diabetes and Clinical Metabolic Research, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel; Düsternbrooker Weg, 17, 24105, Kiel, Germany. matthias.laudes@uksh.de.; Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany. matthias.laudes@uksh.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Sep 02; Vol. 12 (1), pp. 14935. Date of Electronic Publication: 2022 Sep 02.
DOI: 10.1038/s41598-022-18354-x
Abstrakt: Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Comparing T2D subjects with and without DPP4i treatment, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide secreted by adipose tissue macrophages acting pro-inflammatory in various diseases. We therefore examined sFRP5 levels in patients hospitalised for severe COVID-19 and found significant lower levels compared to healthy controls. Since sFRP5 might consequently be a molecular link for the beneficial effects of DPP4i in COVID-19, we further aimed to identify the exact source of sFRP5 in adipose tissue on cellular level. We therefore isolated pre-adipocytes, mature adipocytes and macrophages from adipose tissue biopsies and performed western-blotting. Results showed a sFRP5 expression specifically in mature adipocytes of subcutaneous and omental adipose tissue. In summary, our data suggest that DPP4i increase serum levels of anti-inflammatory sFRP5 which might be beneficial in COVID-19, reflecting a state of sFRP5 deficiency.
(© 2022. The Author(s).)
Databáze: MEDLINE
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