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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« Thermodynamics of Life | Main | A Timeline from Cell »

February 7, 2014

Irisin and Metabolism - A New Target Emerges

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Posted by Derek

Here's something for metabolic disease people to think about: there's a report adding to what we know about the hormone irisin, secreted from muscle tissue, that causes some depots of white adipose tissue to become more like energy-burning brown fat. In the late 1990s, there were efforts all across the drug industry to find beta-3 adrenoceptor agonists to stimulate brown fat for weight loss and dyslipidemia. None of them ever made it through, and thus the arguments about whether they would actually perform as thought were never really settled. One of the points of contention was how much responsive brown adipose tissue adults had available, but I don't recall anything suspecting that it could be induced. In recent years, though, it's become clear that a number of factors can bring on what's been called "beige fat".

Irisin seems to be released in response to exercise, and is just upstream of the important transcriptional regulator PGC-1a. In fact, release of irisin might be the key to a lot of the beneficial effects of exercise, which would be very much worth knowing. In this study, a stabilized version of it, given iv to rodents, had very strong effects on body weight and glucose tolerance, just the sort of thing a lot of people could use.

One of the very interesting features of this area, from a drug discovery standpoint, is that no one has identified the irisin receptor just yet. Look for headlines on that one pretty soon, though - you can bet that a lot of people are chasing it as we speak.

Update: are human missing out on this, compared to mice and other species?

Comments (14) + TrackBacks (0) | Category: Biological News | Diabetes and Obesity


COMMENTS

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."

Permalink to Comment

2. Erebus on February 7, 2014 10:36 AM writes...

@1 -- I also recall seeing that. The position taken in that article seems pretty well-founded to me. Whether or not irisin has any beneficial effects in humans is still, I think, an open question.

Permalink to Comment

3. Anonymous on February 7, 2014 10:52 AM writes...

Ember Therapeutics is working on this through licensing agreements with Dana Farber Cancer Institute.

Permalink to Comment

4. Ted on February 7, 2014 11:31 AM writes...

Hi Derek:

Did you come across the adipose metabolism paper by following England's thermodynamic theory of life, or was it the other way around...?

+1 for "Thermodynamics Friday".

-t

Permalink to Comment

5. barry on February 7, 2014 12:32 PM writes...

since the first papers on irisin came out, we've learned that brown adipose tissue derives from a precursor to myoblasts, not a precursor of white adipose tissue. Although they have fatty globules on common, they're not close kin.

Permalink to Comment

6. SteveM on February 7, 2014 1:59 PM writes...

Re:"In fact, release of irisin might be the key to a lot of the beneficial effects of exercise....a stabilized version of it, given iv to rodents, had very strong effects on body weight and glucose tolerance, just the sort of thing a lot of people could use."

Or they could exercise...

Permalink to Comment

7. Lu on February 7, 2014 2:00 PM writes...

Sorry to post off-topic, but Derek, what do you make of that?
This story says a university professor was harassed by chemical company for pursuing research on dangers of their product:


http://www.newyorker.com/reporting/2014/02/10/140210fa_fact_aviv?currentPage=all

Permalink to Comment

8. gippgig on February 7, 2014 2:24 PM writes...

Someone should search for individuals with a reverse mutation of the irisin start codon back to ATG.

Permalink to Comment

9. luysii on February 7, 2014 3:23 PM writes...

It's about time we all realize that just about every tissue in the body is really an endocrine organ -- something that releases molecules into the blood to affect other organs. There are at least 20 fat hormones (called adipokines). Now we have muscle releasing irisin.

This makes life more complicated, but certainly more interesting.

Permalink to Comment

10. jhb on February 7, 2014 4:51 PM writes...

Read a recent article on this topic http://www.nytimes.com/2012/01/25/health/brown-fat-burns-ordinary-fat-study-finds.html

Is the suggestion that it is shivering that triggers this process (and that exercise merely simulates shivering) plausible?


Permalink to Comment

11. Anonymous on February 7, 2014 8:45 PM writes...

The original Spiegelman Nature article that reported the discovery of irisin had serious flaws. I remember noting a number of issues at the time, not that I was able to convince others to not waste time on trying to reproduce the work (which, sure enough, they were unable to reproduce). This article (not by me) did a great job of highlighting these issues http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774709/

It was quite the coincidence last year that the obesity fraud paper, which claimed to have discovered 2 novel adipokines and was discussed in this forum, just happened to have targeted Spiegelman http://pipeline.corante.com/archives/2013/09/26/an_unknown_author_with_someone_elses_work_why.php

Make of it what you will!

Permalink to Comment

12. Pennpenn on February 9, 2014 8:05 PM writes...

@6-SteveM: That's presuming they aren't already. Or are capable. And maybe figuring out how this works will help us understand more about how metabolism works so that exercising helps people more.

While I'm not saying that people should expect others to solve all their problems, saying "Or they could just X" is a very poor way of looking at research into metabolism and weight related issues.

Permalink to Comment

13. ESIMS on February 10, 2014 4:39 PM writes...

Irisin and FGF21 Are Cold-Induced Endocrine Activators of Brown Fat Function in Humans

http://www.sciencedirect.com/science/article/pii/S1550413114000060

from the SI:
analyzed using western blot against FNDC5 antibody (Abcam, Cambridge, U.K.), which detects both FNDC5 and irisin (Bostrom et al., 2012). Please note: the anti-FNDC5 antibody (ab93373) used in the experiments is no longer available at Abcam. It has been substituted by ab131390.

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14. Spiny Norman on February 18, 2014 8:27 PM writes...

@11 — That piece by Erickson is devastating. He's a careful and rigorous biochemist of the old school (though his ideas about tubulin nucleation have not fared well). When he raises his voice and says experiments are shoddy, I listen.

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