Arch. Endocrinol. Metab. 2021;65(2):121-123
Irisin and its relationship with metabolic health: more questions than answers
DOI: 10.20945/2359-3997000000355
Irisin is a proliferator-activated receptor-gamma coactivator-1α (PGC-1α)-dependent myokine. It was identified in 2012 and, at that time, received a lot of attention due to the hypothesis that drives the browning of white adipose tissue, leading to metabolic benefits and increased thermogenesis (,). The original research suggested that irisin is secreted after cleavage of the extracellular domain of a precursor transmembrane protein called fibronectin type III domain-containing protein 5 (FNDC5) in response to exercise (). As such, irisin could be an important effector of the metabolic effects of physical activity in human health and a potential therapeutic target for diseases, such as obesity and type 2 diabetes (). Nevertheless, further studies have questioned the relevance or even the existence of irisin in humans (,). These issues have arisen due to several reasons, as the start codon (ATA) of the human FNDC5 (which is different from the canonical start codon ATG, present in other mammals) is generally associated with very low protein synthesis. Besides, there are claims that many of the commercially available assays for irisin detection lack specificity (,). Moreover, there is no evidence, in the available assays, that irisin is secreted in humans after regular physical activity practice, or that it has any effect on browning, in the available assays () and most trials shows that its levels are generally increased in obesity and metabolic syndrome (,,–).
In this issue of the Archives of Endocrinology and Metabolism, two articles show new data concerning the controversial field of irisin levels in humans and add more pieces to the puzzle, although we clearly still have more questions than answers (,).
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