Diabetologie und Stoffwechsel 2021; 16(S 01): S70-S71
DOI: 10.1055/s-0041-1727512
10. Adipositastherapie/Metabolische Chirurgie

Circulating sDPP-4 is increased in human subjects with obesity and related metabolic abnormalities and is altered in subjects hospitalized for severe COVID-19 infection

N Rohmann
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
K Schlicht
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
C Geisler
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
T Hollstein
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
C Knappe
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
L Krause
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
S Hagen
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
A Beckmann
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
AK Seoudy
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
P Wietzke-Braun
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
K Hartmann
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
D Schulte
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
K Türk
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
,
J Beckmann
2   UKSH Kiel, University of Kiel, Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, Kiel, Germany
,
W von Schönfels
2   UKSH Kiel, University of Kiel, Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, Kiel, Germany
,
FA Hägele
3   Christian-Albrechts-University of Kiel, Institut of Human Nutrition and Food Science, Kiel, Germany
,
A Bosy-Westphal
3   Christian-Albrechts-University of Kiel, Institut of Human Nutrition and Food Science, Kiel, Germany
,
J Schwarz
4   UKSH Kiel, University of Kiel, Institute of Clinical Molecular Biology, Institute of Clinical Chemistry, Kiel, Germany
,
F Tran
5   UKSH Kiel, University of Kiel, Institute of Clinical Molecular Biology; Division of Pneumology, Department of Medicine 1, Kiel, Germany
,
D Schunk
6   UKSH Kiel, University of Kiel, Interdisciplinary Emergency Center, Kiel, Germany
,
R Junker
7   UKSH Kiel, University of Kiel, Institute of Clinical Chemistry, Kiel, Germany
,
T Bahmer
8   UKSH Kiel, University of Kiel, Division of Pneumology, Department of Medicine 1, Kiel, Germany
,
P Rosenstiel
9   UKSH Kiel, University of Kiel, Institute of Clinical Molecular Biology, Kiel, Germany
,
A Franke
9   UKSH Kiel, University of Kiel, Institute of Clinical Molecular Biology, Kiel, Germany
,
S Schreiber
10   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1; Institute of Clinical Molecular Biology, Kiel, Germany
,
M Laudes
1   UKSH Kiel, University of Kiel, Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, Kiel, Germany
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Aims Dipeptidylpeptidase is a key regulator of the incretin system. Initially, it’s soluble form (sDPP-4) was described as an adipokine mediating metabolic inflammation. This is recently questioned in mechanistic rodent studies. To further clarify sDPP-4’s role in physiology and metabolic diseases, we examined sDPP-4 in a large human cohort and during weight-loss interventions. Like ACE2, sDPP-4 serves as a binding partner for certain corona-like viruses enabling virus entry. As metabolic diseases are major risk factors for the COVID-19 pandemic, we additionally examined sDPP-4 in patients suffering severe Sars-CoV-2 infection.

Methods sDPP-4 serum concentrations were measured using ELISA and related to various metabolic variables. Using a case-control-design, sDPP-4 was assessed in acute COVID-19 and sepsis infection.

Results sDPP-4 increased with body weight, insulin resistance and hypertriglyceridemia but reduced in type 2 diabetes and arterial hypertension. Altered serum concentrations appeared with impaired liver and kidney but not cardiac function. No association to systemic inflammation was observed. Having found increased sDPP-4 in obesity, surgical (gastric bypass/sleeve gastrectomy) and non-surgical weight-loss interventions revealed a significant association of sDPP-4 with the improvement of liver function but neither with changes in body weight nor fat mass. Complementary, the case control study revealed reduced sDPP-4 concentrations specific for COVID-19 infection.

Conclusions We suggest that sDPP-4 is rather related to hepatic abnormalities in obesity than primarily functioning as an adipokine. sDPP-4 is implicated in glucose and lipid metabolism, but not fundamentally in systemic inflammation. Additional to ACE-2, sDPP-4 might also have a regulatory role in COVID-19 infection.


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  • Literatur

  • Rohmann N, Schlicht K, Corinna G, Hollstein T, Knappe C, Krause L, Hagen S, Beckmann A, Seoudy AK, Wietzke-Braun P, Hartmann K, Schulte D, Türk K, Beckmann J, von Schönfels W, Hägele FA, Bosy-Westphal A, Franke A, Schreiber S, Laudes M. Circulating sDPP-4 is increased in obesity and insulin resistance but is not related to systemic metabolic inflammation. J Clin Endocrinol Metab 2020; Oct 21: dgaa758. DOI: 10.1210/clinem/dgaa758. Epub ahead of print. PMID: 33084870.
    CrossrefPubMedGoogle Scholar
  • Schlicht K, Rohmann N, Geisler C, Hollstein T, Knappe C, Hartmann K, Schwarz J, Tran F, Schunk D, Junker R, Bahmer T, Rosenstiel P, Schulte D, Türk K, Franke A, Schreiber S, Laudes M. Circulating levels of soluble Dipeptidylpeptidase-4 are reduced in human subjects hospitalized for severe COVID-19 infections. Int J Obes (Lond) 2020; Nov; 44 (11) 2335-2338. DOI: 10.1038/s41366-020-00689-y. Epub 2020 Sep 21. PMID: 32958905; PMCID: PMC7503441.
    CrossrefPubMedGoogle Scholar
  • Varin EM, Mulvihill EE, Beaudry JL, Pujadas G, Fuchs S, Tanti JF, Fazio S, Kaur K, Cao X, Baggio LL, Matthews D, Campbell JE, Drucker DJ. Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab 2019; Feb 5; 29 (02) 320-334.e5. DOI: 10.1016/j.cmet.2018.10.001. Epub 2018 Nov 1. PMID: 30393019.
    CrossrefPubMedGoogle Scholar
  • Inn KS, Kim Y, Aigerim A, Park U, Hwang ES, Choi MS, Kim YS, Cho NH. Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus. Virology 2018; 518: 324-327. DOI: 10.1016/j.virol.2018.03.015. Epub 2018 Mar 26. PMID: 29587190; PMCID: PMC7112025.
    CrossrefPubMedGoogle Scholar
  • Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020; Apr 16; 181 (02) 271-280.e8. DOI: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5. PMID: 32142651; PMCID: PMC7102627.
    CrossrefPubMedGoogle Scholar

Publication History

Article published online:
06 May 2021

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  • Literatur

  • Rohmann N, Schlicht K, Corinna G, Hollstein T, Knappe C, Krause L, Hagen S, Beckmann A, Seoudy AK, Wietzke-Braun P, Hartmann K, Schulte D, Türk K, Beckmann J, von Schönfels W, Hägele FA, Bosy-Westphal A, Franke A, Schreiber S, Laudes M. Circulating sDPP-4 is increased in obesity and insulin resistance but is not related to systemic metabolic inflammation. J Clin Endocrinol Metab 2020; Oct 21: dgaa758. DOI: 10.1210/clinem/dgaa758. Epub ahead of print. PMID: 33084870.
    CrossrefPubMedGoogle Scholar
  • Schlicht K, Rohmann N, Geisler C, Hollstein T, Knappe C, Hartmann K, Schwarz J, Tran F, Schunk D, Junker R, Bahmer T, Rosenstiel P, Schulte D, Türk K, Franke A, Schreiber S, Laudes M. Circulating levels of soluble Dipeptidylpeptidase-4 are reduced in human subjects hospitalized for severe COVID-19 infections. Int J Obes (Lond) 2020; Nov; 44 (11) 2335-2338. DOI: 10.1038/s41366-020-00689-y. Epub 2020 Sep 21. PMID: 32958905; PMCID: PMC7503441.
    CrossrefPubMedGoogle Scholar
  • Varin EM, Mulvihill EE, Beaudry JL, Pujadas G, Fuchs S, Tanti JF, Fazio S, Kaur K, Cao X, Baggio LL, Matthews D, Campbell JE, Drucker DJ. Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab 2019; Feb 5; 29 (02) 320-334.e5. DOI: 10.1016/j.cmet.2018.10.001. Epub 2018 Nov 1. PMID: 30393019.
    CrossrefPubMedGoogle Scholar
  • Inn KS, Kim Y, Aigerim A, Park U, Hwang ES, Choi MS, Kim YS, Cho NH. Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus. Virology 2018; 518: 324-327. DOI: 10.1016/j.virol.2018.03.015. Epub 2018 Mar 26. PMID: 29587190; PMCID: PMC7112025.
    CrossrefPubMedGoogle Scholar
  • Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020; Apr 16; 181 (02) 271-280.e8. DOI: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5. PMID: 32142651; PMCID: PMC7102627.
    CrossrefPubMedGoogle Scholar