Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes.
Adipocyte 10, 216-231 (2021)
Verlagsversion Forschungsdaten DOI
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adipose Tissue ; Internalization ; Kallikrein ; Obesity ; Proteolysis ; Serpin; Protein Transduction Domain; Adipose-tissue Inflammation; Mitotic Clonal Expansion; Heparan-sulfate; Kallikrein 7; Tat Protein; C Inhibitor; Beta-sheet; Hiv-1 Tat; Obesity
ISSN (print) / ISBN 2162-3945
Quellenangaben Band: 10, Heft: 1, Seiten: 216-231
Verlag Landes Bioscience
Verlagsort 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen Deutsche Forschungsgemeinschaft