First discovered in 2011, irisin was described as a hormone produced by exercise. Since its discovery, the founding scientists and others speculated it could be a perfect drug target for obesity and metabolic disease, while the media immediately hyped the "exercise hormone" with inflated adjectives like magical and powerful. Yesterday hopes were dashed, however, when an international team of scientists called all prior research into question with evidence against irisin's very existence.

“Our data indicate that all previously published assays based on commercial ELISAs… were reporting unknown cross-reacting proteins,” wrote the authors in their new research. Irisin, they say, may not even exist.

The Harvard researchers who discovered irisin originally referred to it as a myokine — a type of protein that aids communication between muscles and other tissues (including fat tissue). Triumphant, they named irisin after Iris, the messenger goddess in Greek mythology, and theorized it turns white adipose tissue (fat) brown, while transforming chemical energy into heat. For a few sunny years, the scientists were convinced their new exercise-hormone might decrease a person's susceptibility to obesity, diabetes, and other health problems.

Looking over the many studies prompted by the original, a thoughtful team of scientists hailing from Germany, Norway, the United States, and Switzerland developed a simple hypothesis. They wondered whether the laboratory test used to establish the presence of irisin was specific and sensitive enough. Is it possible the immunoassays could be reporting cross-reacting proteins and not irisin itself?

Testing the Test

An immunoassay (commonly called an ELISA or enzyme-linked immuno assay) is a widely used biochemical test that measures the presence or concentration of a macromolecule (in this case, proteins) in a solution. To perform this test, an antibody or immunoglobulin is needed — this is what the protein in question will bind to and then be measured by the scientists. There’s one big problem in using these tests to detect irisin, according to the authors of the present study. Potentially, the necessary use of antibodies might provoke cross-reactions with other proteins; the test, then, might detect the presence of unknown proteins and mistakenly interpret them as irisin.

And so the team set to work investigating not the results of tests from prior studies, but the tests themselves. In particular, they examined four antibodies, three of which were used in ELISAs used in more than 80 published studies on irisin. They found the four antibodies had "prominent cross-reactions" with non-irisin proteins.

Sadly, they conclude, “Our results provide experimental evidence for irisin being a myth.” Finally challenged, this new and wonderful hormone — mythical, powerful, unquestioned — takes a dive.

Source: Albrecht E, Norheim F, Thiede B, et al. Irisin — a myth rather than an exercise-inducible myokine. Scientific Reports. 2015.