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Irisin Fights Back

Irisin is the so-called “exercise hormone”, and it’s been the subject of a lot of controversy since its discovery. Not everyone is convinced that it even exists in humans, and a paper earlier this year flat-out called it a myth, which is something that you don’t see very often in the scientific literature.

Now the Spiegelman group, irisin’s discoverers, have fired back. This paper reports the quantification of the hormone in circulating human blood, via fairly advanced analytical techniques, and maintains that it does indeed exist (even though its gene has a funny-looking start codon), and that its levels are increased by exercise. Here’s the press release, if you don’t have access to the paper.

So the ball has been hit back across the net – for now, it looks like irisin is in there, but you really have to bear down to see it, and that antibody-based detection is not the way to go. The tandem mass-spec method that the Spiegelman group has used here is not exactly cheap or convenient, but there’s no requirement that nature make it easy for any of us. We’ll see what the response is, and how long it takes to arrive. . .

11 comments on “Irisin Fights Back”

  1. Imaging guy says:

    When ENCODE consortium published papers claiming 80% of human genome is transcribed and therefore functional (not junk DNA), many researchers criticized them saying it was just transcriptional noise. I wonder whether there is any non-functional proteins due to translational or post translational noise in human proteome.

  2. milkshake says:

    So, you have an unconfirmed, presumably hormone-like protein with baseline ∼3.6 ng/mL that is boosted only up to 4.3 ng/mL after vigorous exercise, and you also presume “a complex regulation mechanism” due to non-canonical start codon, and when you ave to use a rather elaborate MS technique to quantify it – a technique that can have its limits of reproducibility. To me this sounds like a tentative proof at best, I can imagine a many things that could go wrong with this chain of reasoning. Someone will need to produce human irisin by synthesis and put it into primates (or better yet, healthy human volunteers) otherwise this controversy will go on, like chasing a ghost.

  3. George Traitor Tenet says:

    Nice play on thread title for this alleged protein again, oh lover of witty wording.

  4. Falanx says:

    @Milkshake

    Yes, only a *20%* increase. Nothing at all really.

  5. simpl says:

    “Not everyone is convinced that it even exists in humans”
    That’s a motivator – I remember when dopamine and GABA didn’t exist in animals, let alone man, and the resulting drug sales were the best proof that the theories had to change.

  6. a. nonymaus says:

    I haven’t seen a call-out like that in the literature since the dust-up over non-thermal microwave effects, which also had a most excellent TOC graphic:
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201204103/abstract

  7. loving_it says:

    @a. nonymaus Love it! Thanks for sharing

  8. Curt F. says:

    I’ve done a fair bit of mass spec proteomics back in the day, and their identification of irisin is compelling. The detected concentration range for irisin is several orders of magnitude higher in concentration than hormones like insulin or glucagon, as figure 2D of the paper shows quite clearly. I’d be very surprised if the finding that irisin exists in the plasma of (at least some) human subjects is meaningfully challenged after this paper.

    The measured increase in response to exercise is another thing entirely. It is small and from a quick look it doesn’t look like they designed a paired experiment. If natural human levels of irisin vary widely due to extraneous factors, that noise could mask a quite profound increase in irisin on exercise (perhaps up to 50% as estimated from eyeballing figure 2C, in which blissfully the authors plot all of their raw data points, avoiding the horrible yet all-too-common practice of making bar graphs.) But that’s speculative and the exercise-dependent increase might be just about opposite with a better-designed experiment. And even if the 20% increase is correct, that doesn’t say much about the biological meaning. Is the 20% increase in concentration enough to modulate some (set of) receptors somewhere?

    So irisin is almost certainly really found in some humans. What it’s function is, and whether it is really response to exercise, is another thing entirely.

  9. David says:

    @ milkshake – the use of AQUA peptides and MS2 to for identification and quantitation is as close to gold currency as it can be in science.

  10. James Wardely says:

    @milkshake as they say, haters gonna hate LOL.

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