Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling
- Yuan Zhang1,2,
- Rui Li1,2,
- Yan Meng1,
- Shiwu Li3,
- William Donelan3,
- Yan Zhao2,
- Lei Qi2,
- Mingxiang Zhang2,
- Xingli Wang2,
- Taixing Cui2,4⇑,
- Li-Jun Yang3⇑ and
- Dongqi Tang1,2,4⇑
- 1Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan, People’s Republic of China
- 2Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, People’s Republic of China
- 3Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL
- 4Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC
- Corresponding authors: Dongqi Tang, , Taixing Cui, , and Li-Jun Yang, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1106/-/DC1.
See accompanying commentary, p. 381.
- Received July 16, 2013.
- Accepted October 9, 2013.
- © 2014 by the American Diabetes Association.
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