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

Abhirup Shaw; Beáta B Tóth; Róbert Király; Rini Arianti; István Csomós; Szilárd Póliska; Attila Vámos; Ilma R Korponay-Szabó; Zsolt Bacso; Ferenc Győry; László Fésüs; Endre Kristóf

doi:10.3389/fcell.2021.737872

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

Front Cell Dev Biol. 2021 Oct 11:9:737872. doi: 10.3389/fcell.2021.737872. eCollection 2021.

Authors

Abhirup Shaw^{1

2}, Beáta B Tóth¹, Róbert Király¹, Rini Arianti^{1

2}, István Csomós³, Szilárd Póliska⁴, Attila Vámos^{1

2}, Ilma R Korponay-Szabó⁵, Zsolt Bacso^{3

6}, Ferenc Győry⁷, László Fésüs¹, Endre Kristóf¹

Affiliations

¹ Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
² Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary.
³ Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁴ Genomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁵ Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁶ Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.
⁷ Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Abstract

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.

Keywords: CXCL1; NFκB; adipose tissue; angiogenesis; cytokines; integrins; irisin; obesity.