Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes

Vaspin expression and function is related to metabolic disorders and comorbidities of obesity. In various cellular and animal models of obesity, diabetes and atherosclerosis vaspin has shown beneficial, protective and/or compensatory action. While testing proteases for inhibition by vaspin, we notic...

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Main Authors: Catherine A. Tindall, Estelle Erkner, Jan Stichel, Annette G. Beck-Sickinger, Anne Hoffmann, Juliane Weiner, John T. Heiker
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Adipocyte
Subjects:
Online Access:http://dx.doi.org/10.1080/21623945.2021.1910154
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spelling doaj-fe36d77df59a4c4bb48c8f8ac88734b02021-05-06T16:05:14ZengTaylor & Francis GroupAdipocyte2162-39452162-397X2021-01-0110121623110.1080/21623945.2021.19101541910154Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytesCatherine A. Tindall0Estelle Erkner1Jan Stichel2Annette G. Beck-Sickinger3Anne Hoffmann4Juliane Weiner5John T. Heiker6Leipzig UniversityLeipzig UniversityLeipzig UniversityLeipzig UniversityHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigUniversity of Leipzig Medical CenterLeipzig UniversityVaspin expression and function is related to metabolic disorders and comorbidities of obesity. In various cellular and animal models of obesity, diabetes and atherosclerosis vaspin has shown beneficial, protective and/or compensatory action. While testing proteases for inhibition by vaspin, we noticed specific cleavage within the vaspin N-terminus and sequence analysis predicted cell-penetrating activity for the released peptides. These findings raised the question whether these proteolytic peptides exhibit biological activity. We synthesized various N-terminal vaspin peptides to investigate cell-penetrating activity and analyse uptake mechanisms. Focusing on adipocytes, we performed microarray analysis and functional assays to elucidate biological activities of the vaspin–derived peptide, which is released by KLK7 cleavage (vaspin residues 21-30; VaspinN). Our study provides first evidence that proteolytic processing of the vaspin N-terminus releases cell-penetrating and bioactive peptides with effects on adipocyte biology. The VaspinN peptide increased preadipocyte proliferation, interfered with clonal expansion during the early stage of adipogenesis and blunted adrenergic cAMP-signalling, downstream lipolysis as well as insulin signalling in mature adipocytes. Protease-mediated release of functional N-terminal peptides presents an additional facet of vaspin action. Future studies will address the mechanisms underlying the biological activities and clarify, if vaspin-derived peptides may have potential as therapeutic agents for the treatment of metabolic diseases.http://dx.doi.org/10.1080/21623945.2021.1910154adipose tissueinternalizationobesityproteolysiskallikreinserpin
collection DOAJ
language English
format Article
sources DOAJ
author Catherine A. Tindall
Estelle Erkner
Jan Stichel
Annette G. Beck-Sickinger
Anne Hoffmann
Juliane Weiner
John T. Heiker
spellingShingle Catherine A. Tindall
Estelle Erkner
Jan Stichel
Annette G. Beck-Sickinger
Anne Hoffmann
Juliane Weiner
John T. Heiker
Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
Adipocyte
adipose tissue
internalization
obesity
proteolysis
kallikrein
serpin
author_facet Catherine A. Tindall
Estelle Erkner
Jan Stichel
Annette G. Beck-Sickinger
Anne Hoffmann
Juliane Weiner
John T. Heiker
author_sort Catherine A. Tindall
title Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
title_short Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
title_full Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
title_fullStr Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
title_full_unstemmed Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
title_sort cleavage of the vaspin n-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes
publisher Taylor & Francis Group
series Adipocyte
issn 2162-3945
2162-397X
publishDate 2021-01-01
description Vaspin expression and function is related to metabolic disorders and comorbidities of obesity. In various cellular and animal models of obesity, diabetes and atherosclerosis vaspin has shown beneficial, protective and/or compensatory action. While testing proteases for inhibition by vaspin, we noticed specific cleavage within the vaspin N-terminus and sequence analysis predicted cell-penetrating activity for the released peptides. These findings raised the question whether these proteolytic peptides exhibit biological activity. We synthesized various N-terminal vaspin peptides to investigate cell-penetrating activity and analyse uptake mechanisms. Focusing on adipocytes, we performed microarray analysis and functional assays to elucidate biological activities of the vaspin–derived peptide, which is released by KLK7 cleavage (vaspin residues 21-30; VaspinN). Our study provides first evidence that proteolytic processing of the vaspin N-terminus releases cell-penetrating and bioactive peptides with effects on adipocyte biology. The VaspinN peptide increased preadipocyte proliferation, interfered with clonal expansion during the early stage of adipogenesis and blunted adrenergic cAMP-signalling, downstream lipolysis as well as insulin signalling in mature adipocytes. Protease-mediated release of functional N-terminal peptides presents an additional facet of vaspin action. Future studies will address the mechanisms underlying the biological activities and clarify, if vaspin-derived peptides may have potential as therapeutic agents for the treatment of metabolic diseases.
topic adipose tissue
internalization
obesity
proteolysis
kallikrein
serpin
url http://dx.doi.org/10.1080/21623945.2021.1910154
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