irisin

Irisin is a peptide hormone proposed to be a myokine released into the circulation by skeletal muscle in response to physical exercise. It is produced through proteolytic cleavage of the transmembrane protein fibronectin type III domain-containing protein 5 (FNDC5), and was described as a circulating factor that links muscle activity to metabolic adaptation.

In animal models, irisin was reported to induce browning of white adipose tissue, increasing expression of thermogenic proteins such as UCP1 and enhancing energy expenditure. This led to interest in its potential role in regulating body weight, glucose homeostasis, and lipid metabolism. Evidence in humans has been less consistent, with studies reporting variable circulating levels and mixed associations with obesity or insulin resistance. Additional reported effects include modulation of brain-derived factors and possible influences on bone and neuronal health, though these findings require replication.

Controversies center on the detectability and physiological relevance of irisin in humans. Difficulties with assay specificity, issues with measurement of irisin in blood, and debate over the translation of FNDC5 in humans (the human FNDC5 start codon is non-AUG in some reports) have tempered enthusiasm. A receptor for irisin has been proposed in some studies (for example, integrin receptors), but consensus and independent replication are lacking.

Today, irisin remains a topic of active investigation. While it is widely cited as a muscle-derived signal that could influence adipose tissue and metabolism, there is no established clinical role or approved therapeutic application, and the field continues to evaluate its biology, measurement methods, and potential translational relevance.