Irisin - a myth rather than an exercise-inducible myokine.
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.
Institute for Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany.
Elke
E
Albrecht
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Frode
F
Norheim
The Biotechnology Centre of Oslo, University of Oslo, 0317 Oslo, Norway.
Bernd
B
Thiede
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Torgeir
T
Holen
Department of Cell Biology, Duke University, Durham, NC 27710, USA.
Tomoo
T
Ohashi
Institute for Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany.
Lisa
L
Schering
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Sindre
S
Lee
Institute of Genome Biology, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany.
Julia
J
Brenmoehl
Swiss Institute of Equine Medicine (ISME), Vetsuisse Faculty, University of Berne, 1580 Avenches, Switzerland.
Selina
S
Thomas
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Christian A
CA
Drevon
Department of Cell Biology, Duke University, Durham, NC 27710, USA.
Harold P
HP
Erickson
Institute for Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany.
Steffen
S
Maak
D000818:Animals; D016477:Artifacts; D001774:Blood Chemical Analysis / Q000379:methods; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D015444:Exercise / Q000502:physiology*; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D016207:Cytokines; C577593:FNDC5 protein, human; C571428:FNDC5 protein, mouse; D005353:Fibronectins