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Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway

Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed “batokines”. Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primar...

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Autores principales: Shaw, Abhirup, Tóth, Beáta B., Király, Róbert, Arianti, Rini, Csomós, István, Póliska, Szilárd, Vámos, Attila, Korponay-Szabó, Ilma R., Bacso, Zsolt, Győry, Ferenc, Fésüs, László, Kristóf, Endre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542801/
https://www.ncbi.nlm.nih.gov/pubmed/34708041
http://dx.doi.org/10.3389/fcell.2021.737872
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author Shaw, Abhirup
Tóth, Beáta B.
Király, Róbert
Arianti, Rini
Csomós, István
Póliska, Szilárd
Vámos, Attila
Korponay-Szabó, Ilma R.
Bacso, Zsolt
Győry, Ferenc
Fésüs, László
Kristóf, Endre
author_facet Shaw, Abhirup
Tóth, Beáta B.
Király, Róbert
Arianti, Rini
Csomós, István
Póliska, Szilárd
Vámos, Attila
Korponay-Szabó, Ilma R.
Bacso, Zsolt
Győry, Ferenc
Fésüs, László
Kristóf, Endre
author_sort Shaw, Abhirup
collection PubMed
description Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed “batokines”. Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines, CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 h irisin treatment. Gene expression data indicated upregulation of the NFκB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IκBα protein level, respectively. Continuous blocking of the NFκB pathway, using a cell permeable inhibitor of NFκB nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.
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spelling pubmed-85428012021-10-26 Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway Shaw, Abhirup Tóth, Beáta B. Király, Róbert Arianti, Rini Csomós, István Póliska, Szilárd Vámos, Attila Korponay-Szabó, Ilma R. Bacso, Zsolt Győry, Ferenc Fésüs, László Kristóf, Endre Front Cell Dev Biol Cell and Developmental Biology Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed “batokines”. Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines, CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 h irisin treatment. Gene expression data indicated upregulation of the NFκB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IκBα protein level, respectively. Continuous blocking of the NFκB pathway, using a cell permeable inhibitor of NFκB nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization. Frontiers Media S.A. 2021-10-11 /pmc/articles/PMC8542801/ /pubmed/34708041 http://dx.doi.org/10.3389/fcell.2021.737872 Text en Copyright © 2021 Shaw, Tóth, Király, Arianti, Csomós, Póliska, Vámos, Korponay-Szabó, Bacso, Győry, Fésüs and Kristóf. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Shaw, Abhirup
Tóth, Beáta B.
Király, Róbert
Arianti, Rini
Csomós, István
Póliska, Szilárd
Vámos, Attila
Korponay-Szabó, Ilma R.
Bacso, Zsolt
Győry, Ferenc
Fésüs, László
Kristóf, Endre
Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
title Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
title_full Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
title_fullStr Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
title_full_unstemmed Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
title_short Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
title_sort irisin stimulates the release of cxcl1 from differentiating human subcutaneous and deep-neck derived adipocytes via upregulation of nfκb pathway
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542801/
https://www.ncbi.nlm.nih.gov/pubmed/34708041
http://dx.doi.org/10.3389/fcell.2021.737872
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