Irisin and FGF21 are cold induced endocrine activators of brown fat function in humans.
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.
Cell metabolism