Irisin stimulates the release of CXCL1 from differentiating human subcutaneous and deep-neck derived adipocytes via upregulation of NFκB pathway

Abstract

Thermogenic brown and beige adipocytes play an important role 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 hours 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 "batokine", CXCL1, via upregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.

Olanzapine induces weight gain in offspring of prenatally exposed poly I:C rats by reducing brown fat thermogenic activity

“…It has been shown that IL-6 released by differentiation of human beige adipocytes promotes the browning of fat (Kristóf et al, 2019). Moreover, irisin promotes the release of CXCL1 stimulated by human subcutaneous and neck differentiated adipocytes through upregulation of the NF-κB pathway (Shaw et al, 2021). However, whether the increase in IL-6 and CXCL1 in mothers has an effect on offspring adipocytes needs to be further investigated.…”

The role of exercise-induced myokines in promoting angiogenesis

“…In the myocardial infarction animal model, irisin treatment also shows myocardial protection, and better angiogenesis at the edge of infarction (Liao et al, 2019). Moreover, irisin can also stimulate adipocyte secretion of CXCL1 and improve endothelial cell adhesion (Shaw et al, 2021). Together, these results suggest that irisin has strong application value in promoting angiogenesis and improving the symptoms of ischemic diseases.…”