JOURNAL ARTICLE

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
Cell Metabolism 2014 February 4, 19 (2): 302-9
24506871
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.

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