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  1. Does Irisin Really Exist in Human Circulation ? JiaQi Chen, Shen Qu*Corresponding author: Shen Qu

    Jiaqi Chen, Shanghai Tenth People's Hospital

    13 May 2015

    Recently, Elke Albrecht et al. [1] questioned about the existence of circulating irisin in human by testing the accuracy of four polyclonal antibodies used in commercial ELISA kits, using Western Blot. The researchers used recombinant non-glycosylated and glycosylated irisin (molecular weights are ~13kDa and ~20kDa, respectively) as positive standards. They found that the antibodies could only detect the recombinant irisin added in PBS, but no band was found at the same position in murine or in human samples. Furthermore, the antibodies were found to have prominent cross-reaction with unspecific proteins, and the bands of similar molecular weight of recombinant irisin at ~16kDa and ~25kDa were further examined by mass spectrometric analysis and proved not to be irisin.

    The debate on the existence of circulating irsin has arisen soon after its discovery, for the published researches assessing irisin levels had a large variation, and the start codon of the human FNDC5 gene was found mutated. This mutation caused low efficiency of transcription and translation of FNDC5, and of course irisin subsequently [2]. The results of Albrecht and colleagues [1] seemed to give strong evidence  to doubt the existence of circulating irisin in humans. However, these  results need to be repeated by other groups and in different populations to confirm their conclusion. And of note, earlier research by Schumacher and colleagues [3] reported that the free cysteine at residue number 59 of irisin causes it to dimerize, and the molecular weight of unglycosylated and glycosylated dimer are 23.5 kDa and 36 kDa, respectively. So the dimerized irisin also needs to be identified more accurately in future studies  to ascertain the existence of irisin and clarify the position and its biological significance.

    Although the variations of irisin concentrations among different studies are large, the published data had consistent evidence supporting that irisin may be a compensative response to insulin resistance and other metabolic disturbances associated with obesity, as  discussed previously [4]. So, we affirm that  in all probability circulating irisin does exist and plays a role in metabolic disorders. Given that the irisin receptor is unknown and the mechanism is unclear, and the antibody used in the initial study [5] was against the aa 149-178, the C-terminal of FNDC5, which is not cleaved as part of irisin (aa 32-143), the question may lie on how irisin is secreted in to the circulation. In other  words, more definitive studies are needed to establish the presence of irisin by evaluating  which exact fragment of FNDC5 is cleaved and modified to act as “irisin”.


    1.    Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, Lee S, Brenmoehl J, Thomas S, Drevon CA et al: Irisin - a myth rather than an exercise-inducible myokine. Sci Rep 2015, 5:8889.

    2.    Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisloff U, Tjonna AE, Raastad T et al: Evidence against a beneficial effect of irisin in humans. PLoS One 2013, 8(9):e73680.

    3.    Schumacher MA, Chinnam N, Ohashi T, Shah RS, Erickson HP: The structure of irisin reveals a novel intersubunit beta-sheet fibronectin type  III (FNIII) dimer: implications for receptor activation. J Biol Chem 2013, 288(47):33738-33744.

    4.    Chen JQ, Huang YY, Gusdon AM, Qu S: Irisin: a new molecular marker and target in metabolic disorder. Lipids Health Dis 2015, 14(1):2.

    5.   Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ et al: A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481(7382):463-468.

    Competing interests

    No Competing Interests