Is Irisin (the exercise hormone) a Greek goddess or a Greek myth?

RunningIrisin, a hormone supposedly produced by exercise, was discovered in 2011 and published in early 2012 in Nature amidst resounding hype and adulation. It had been billed as a substance that could convert white fat into brown fat. It held the potential for weight loss and a host of other problems. However, according to a recent report, a group of scientists cast serious doubts over the very existence of Irisin.

The original paper citing the discovery of Irisin was published in Nature in 2012 by a group of Harvard investigators led by Bruce Spiegelman. It was named after the Greek goddess and messenger Iris and it was supposed to relay instructions from muscles to fat after exercise to burn and not store. This publication led to an outburst among other research groups putting their efforts into trying to elucidate an explanation on the possible role of Irisin in human physiology.

Inspite of lack of convincing evidence and many concerns (one raised by Harold P. Erickson in 2013 in the journal Adipocyte), many groups were convinced about it and so far there have been more than 170 publications on it. Unfortunately, the latest study published in Scientific Reports refutes all the findings of the previous studies claiming its existence to be a myth. “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.

Most of the previous studies looked at the role of the hormone and the parent gene in conditions not just pertaining to exercise but also diabetes, protein and cancer. However, all of them used commercial ELISA kits – a technique that analyzes proteins in a single dish – that eventually proved to be a fatal shortcut. These ELISA kits essentially use an antibody that binds to the protein in question and measured. Now, this international group of researchers who hail from Germany, Norway, Switzerland and USA wondered if this test used to establish the presence of Irisin was specific and sensitive enough. This is because the use of antibodies might provoke cross-reactivity with other proteins which might lead to the detection of unknown proteins and mistakenly interpreted as Irisin.

To test their hypothesis, these scientists examined four antibodies, three of which were used in ELISAs that were reported in more than 80 published studies. Strikingly, they found that the four antibodies had “prominent cross-reactions” with non-Irisin proteins. “Our conclusions make sense, especially in light of the work of other researchers who have shown that the human version of the FNDC5 gene has a deleterious mutation at the beginning,” Erickson said in a press release. “As a result, humans can produce less than 1% of the Irisin present in other species. Humans are essentially a gene knock-out — they can’t produce FNDC5, and therefore they can’t produce Irisin.”

Spiegelman, nevertheless, stands by the existence of Irisin. “The previous identification of human Irisin in blood by mass spectrometry by Celi and colleagues has previously closed the question as to the existence of Irisin [in humans],” he said. “The lack of ability of the current investigators to find circulating Irisin may reflect the sensitivity of the procedures.” Sadly, the very existence of this powerful and magical hormone has taken a dive.

The original publication can be accessed here.

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