Irisin – a myth rather than an exercise-inducible myokine

Abstract

The myokine irisin is supposed to be cleaved from a transmembrane precursor, FNDC5 (fibronectin type III domain containing 5), and to mediate beneficial effects of exercise on human metabolism. However, evidence for irisin circulating in blood is largely based on commercial ELISA kits which are based on polyclonal antibodies (pAbs) not previously tested for cross-reacting serum proteins. We have analyzed four commercial pAbs by Western blotting, which revealed prominent cross-reactivity with non-specific proteins in human and animal sera. Using recombinant glycosylated and non-glycosylated irisin as positive controls, we found no immune-reactive bands of the expected size in any biological samples. A FNDC5 signature was identified at ~20 kDa by mass spectrometry in human serum but was not detected by the commercial pAbs tested. Our results call into question all previous data obtained with commercial ELISA kits for irisin, and provide evidence against a physiological role for irisin in humans and other species.

New insights into the effects of irisin levels in HIV-infected subjects: correlation with adiposity, fat-free mass, and strength parameters

“…Thus, the results of irisin studies in humans should be interpreted with caution, and findings in mice should not be directly translated into humans (29). Moreover, serum irisin was measured by ELISA, which is based on polyclonal antibodies not previously tested for crossreaction with serum proteins (30). However, it has been proposed that the variations in irisin concentrations found with different ELISA kits are consistent across independent studies with different cohorts of patients (31).…”

Horizons in the Pharmacotherapy of Obesity

“…Therefore, it is important not only to acutely activate thermogenesis in brown adipocytes but also to increase their number and their capacity for thermogenesis [64]. Among the approaches being investigated are mimetics of irisin and fibroblast growth factor-21 [65,66], though recent work casts doubt on the role of irisin because many studies have used commercial ELISA kits to detect irisin that cross-react with other proteins [67].…”

Exercise regulation of adipose tissue

“…44 One possible reason for the discrepancies in the effects of exercise training on circulating irisin concentrations is the technique used to measure irisin. Studies have indicated that human irisin antibodies used in commercial ELISA kits may not accurately detect irisin 47,49 because the antibody used was measuring the transmembrane domain of FNDC5 and not the secreted irisin peptide. This may have resulted in an inaccurate measurement of circulating irisin concentration in response to exercise.…”

“…27 While these intriguing data suggested a role for irisin in response to exercise training in both mice and humans, results from several follow up studies came to varying conclusions. 27,33,[43][44][45][46][47][48] These studies have all addressed the questions of whether exercise training increases circulating irisin concentrations and some of the investigations determined if exercise-induced increases in irisin cause a beiging of scWAT in humans. A combined endurance and strengthtraining program in male subjects had no effect on circulating irisin concentrations, 33 although interestingly, and as discussed above, these training programs only resulted in modest, if any increase in beiging of scWAT.…”