Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans
Paul Lee, Joyce D Linderman, Sheila Smith, Robert J Brychta, Juan Wang, Christopher Idelson, Rachel M Perron, Charlotte D Werner, Giao Q Phan, Udai S Kammula, Electron Kebebew, Karel Pacak, Kong Y Chen, Francesco S Celi, Paul Lee, Joyce D Linderman, Sheila Smith, Robert J Brychta, Juan Wang, Christopher Idelson, Rachel M Perron, Charlotte D Werner, Giao Q Phan, Udai S Kammula, Electron Kebebew, Karel Pacak, Kong Y Chen, Francesco S Celi
Abstract
Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest in identifying BAT activators for metabolic benefits. Of particular interest are cytokines capable of fat browning. Irisin, derived from FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in murine white fat. Here we explored whether cold exposure is an afferent signal for irisin secretion in humans and compared it with FGF21, a brown adipokine in rodents. Cold exposure increased circulating irisin and FGF21. We found an induction of irisin secretion proportional to shivering intensity, in magnitude similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment upregulated human adipocyte brown fat gene/protein expression and thermogenesis in a depot-specific manner. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine axis that is exploitable in obesity therapeutics development.
Copyright © 2014 Elsevier Inc. All rights reserved.
Figures
![Figure 1. Validation of immunoblot-detected irisin by…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7647184/bin/nihms-561810-f0001.jpg)
Figure 2. Relationship between irisin, FGF21, BAT…
Figure 2. Relationship between irisin, FGF21, BAT and temperature
Cold exposure resulted in reduction in…
Figure 3. Effects of FNDC5 and/or FGF21…
Figure 3. Effects of FNDC5 and/or FGF21 treatment on gene/protein expression and bioenergenetics of neck…
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- Clinical Trial
- Research Support, N.I.H., Intramural
- Research Support, Non-U.S. Gov't
- Adipocytes / metabolism
- Adipokines / metabolism
- Adipose Tissue, Brown / metabolism
- Adult
- Exercise / physiology*
- Female
- Fibroblast Growth Factors / blood*
- Fibroblast Growth Factors / metabolism
- Fibronectins / blood*
- Fibronectins / metabolism
- Humans
- Male
- Shivering / physiology
- Young Adult
- Adipokines
- FNDC5 protein, human
- Fibronectins
- fibroblast growth factor 21
- Fibroblast Growth Factors
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 2. Relationship between irisin, FGF21, BAT…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7647184/bin/nihms-561810-f0002.jpg)
Figure 3. Effects of FNDC5 and/or FGF21…
Figure 3. Effects of FNDC5 and/or FGF21 treatment on gene/protein expression and bioenergenetics of neck…
![Figure 3. Effects of FNDC5 and/or FGF21…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7647184/bin/nihms-561810-f0003.jpg)
Source: PubMed