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Dr Claude Jean PARIS


Irisin and FGF21 Are Cold-Induced Endocrine Activators of Brown Fat Function in Humans

 Cell Metabolism, Volume 19, Issue 2, 302-309, 4 February 2014

Copyright © 2014 Elsevier Inc. All rights reserved.
10.1016/j.cmet.2013.12.017

Authors

    • Highlights
    • Shivering stimulates irisin secretion in humans
    • Nonshivering cold exposure increases FGF21, which may be a brown adipokine
    • Irisin and/or FGF21 upregulates brown-fat-like program in human adipocytes
    • Exercise may be a shivering mimic exemplifying muscle-fat thermogenic crosstalk

    Summary

    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 withFGF21, 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.

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