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Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling

Authors :
Rui Li
Yan Zhao
Lei Qi
William Donelan
Xingli Wang
Yan Meng
Dongqi Tang
Taixing Cui
Li-Jun Yang
Shiwu Li
Mingxiang Zhang
Yuan Zhang
Source :
Diabetes
Publication Year :
2014
Publisher :
American Diabetes Association, 2014.

Abstract

The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. In some conditions, certain white adipose tissue (WAT) depots are readily convertible to a ‘‘brown-like’’ state, which is associated with weight loss. Irisin, a newly identified hormone, is secreted by skeletal muscles into circulation and promotes WAT “browning” with unknown mechanisms. In the current study, we demonstrated in mice that recombinant irisin decreased the body weight and improved glucose homeostasis. We further showed that irisin upregulated uncoupling protein-1 (UCP-1; a regulator of thermogenic capability of brown fat) expression. This effect was possibly mediated by irisin-induced phosphorylation of the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal–related kinase (ERK) signaling pathways. Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. In addition, irisin also promoted the expression of betatrophin, another newly identified hormone that promotes pancreatic β-cell proliferation and improves glucose tolerance. In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via the p38 MAPK and ERK pathways.

Details

ISSN :
1939327X and 00121797
Volume :
63
Database :
OpenAIRE
Journal :
Diabetes
Accession number :
edsair.doi.dedup.....2bc8cc474869726dce6d6eead421644a
Full Text :
https://doi.org/10.2337/db13-1106