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Is Irisin Real?

In 2012, the Spiegelman lab at Harvard reported a new peptide hormone, irisin (derived from a known precursor, FNDC5), that seemed to be involved in (among other things) brown-fat-like energy usage and the beneficial effects of exercise. There have been questions from other researchers about this work, but even this time last year work was coming out on irisin’s mode of action. (And as of last September, Spiegelman was still vigorously defending it).
But the controversy over these results is getting ready to spill over into the popular press, which was quite enthusiastic back in 2012 (“Harvard Team Finds Exercise Hormone”, the headlines pretty much write themselves). Here’s an article from MedPage Today, which is probably the fullest look at the situation outside of the primary literature or the metabolic research grapevine. It’s prompted by this new paper in Nature‘s open-access journal Scientific Reports, which fires a cannon right over the bow: “Irisin – a myth rather than an exercise-inducible myokine”. That, by the standards of the scientific literature, is the equivalent of pushing over someone’s Harley in front of the biker bar, an unignorable challenge. The authors have a powerful case. They provide evidence that the antibodies used for the ELISA assays that underpin most (all?) of the published irisin work are, in fact, nonspecific. What’s more, even though they pick up a number of other proteins, they don’t actually seem to recognize authentic (synthesized) irisin. Using a better detection system, however, the authors can find no evidence for meaningful amounts of irisin in human blood at all.
Spiegelman will surely have a response to this – you can’t not have a response to a paper like this one. For now, though, the whole idea of irisin seems to be in doubt, and if it’s indeed not real, a lot of people have been wasting their time.

13 comments on “Is Irisin Real?”

  1. demon says:

    I’ve spent some time on a project which tried to identify the Irisin receptor. Our group was supposed to produce mutated Irisin peptides. Thank god I didn’t waste more time on this. Have to inform my old supervisor though about this paper and I guess he might not be amused.

  2. anonymous says:

    This reminds me of the story from Charlie Serhan’s lab at Harvard that lipoxin A4 is a wonderful anti-inflammatory acting as an agonist via FPRL2. The only fly in the ointment was that all the other FPRL2 agonists are proinflammatory mediators… Oh, and that lipoxin A4 is not a ligand for FPRL2… Other than that, it wasn’t a big waste of time that distracted from other efforts that might actually help people one day….

  3. anon for once says:

    But it’s Haaaaarvard, dear.

  4. Anonymous says:

    The following comment in your post of Feb ’14 about Irisin says it all
    1. Anon on February 7, 2014 10:26 AM writes…
    Reminds me of this article:
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0073680
    “FNDC5, the gene encoding the precursor of irisin, is present in rodents and most primates, but shows in humans a mutation in the conserved start codon ATG to ATA.”
    Essentially we’re a gene knockout for iris. Some proteins can be made without the ATG initiation codon, but usually at levels under 1%.
    This is true even if the assays (using ELISA) were specific (which they aren’t).

  5. PorkPieHat says:

    And what happened to Ember Therapeutics, the Third Rock Ventures company that was supposed to make hay with this technology? Im stunned how much money goes down this path…even though this one seemed heavily tranched.
    http://www.fiercebiotech.com/story/third-rocks-faded-ember-gets-resuscitated-merger-deal/2015-03-12

  6. anonymous says:

    I thought only a handful of us knew that lipoxins et al are atrefacts?

  7. hn says:

    Biologists! Please don’t do research only using antibodies.

  8. Paul Brookes says:

    This will come as no surprise whatsoever to anyone who reads PubPeer…
    https://pubpeer.com/publications/D58CD92ADD3D6301612B0C587147F0

  9. George Treason Tenet says:

    Did you deliberately post this on St. Patrick’s Day, oh player-of-words, DL ?

  10. Cellbio says:

    @2,
    Wasted my time too looking at Lxa4 as a licensing opportunity. Demonstrated extensive dose curves showing profound proinflammatory response, bell shaped curve. Shucks, if one plots only the backside, it can look anti-inflammatory. Data was not met with enthusiasm.
    Have met both Sherhan and Spiegelman, same vibe. While talking to room of otherwise smart people they seem to tell stories in a way that cloaks critical thinking. I dont get it.

  11. James Wardely says:

    @2-you talking about the guy who discovered PPARG, PGC1as, PRDM16 and the inflammatory nature of obesity? That same Spiegelman? What have you discovered lately? LOL.

  12. James Wardely says:

    @Cellbio-you talking about the guy who discovered PPARG, PGC1as, PRDM16 and the inflammatory nature of obesity? That same Spiegelman? What have you discovered lately? LOL.

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