Thursday, April 07, 2005

Marathon Mice and PPARd

Press release from The Salk Institute. It is intriguing that any connection is made between this work and athletic performance. Clearly, the scientist's work is aimed at medical intervention and yet the prospects for athletes are implied through the communication. It is a further indication of how the application of pharmaceuticals to sports is sexy enough to spice up scientific research, but that most scientists are not really alarmed by how their work might be used for non-therapeutic purposes. Equally, perhaps Dr Evans is working with WADA to ensure they have tests for any future product that might arrive on the market. While I don't think that this would be enough to deal with the use of dangerous substances in sport, it would be an important development.

Altering steroid receptor genes creates fat burning muscles, resistance to weight gain, and lowered inflammation.


April 04, 2005 La Jalla, CA — The Salk Institute scientist who earlier discovered that enhancing the function of a single protein produced a mouse with an innate resistance to weight gain and the ability to run a mile without stopping, has found new evidence that this protein and a related protein play central roles in the body's complex journey to obesity and offer a new and specific metabolic approach to the treatment of obesity related disease such as Syndrome X (insulin resistance, hyperlipidemia and atherosclerosis).

Dr. Ronald M. Evans, a Howard Hughes Medical Investigator at Salk Institute's Gene Expression Laboratory, presented two new studies Monday, April 4, at Experimental Biology 2005 in the scientific sessions of the American Society for Biochemistry and Molecular Biology.

The studies focus on genes for two of the nuclear hormone receptors that control broad aspects of body physiology, including serving as molecular sensors for numerous fat soluble hormones, Vitamins A and D, and dietary lipids.

The first study focuses on the gene for PPARd, a master regulator that controls the ability of cells to burn fat. When the "delta switch" is turned on in adipose tissue, local metabolism is activated resulting in increased calorie burning. Increasing PPARd activity in muscle produces the "marathon mouse," characterized by super-ability for long distance running.

Marathon mice contain altered muscle composition, which doubles its physical endurance, enabling it to run an hour longer than a normal mouse. Marathon mice contain increased levels of slow twitch (type I) muscle fiber, which confers innate resistance to weight gain, even in the absence of exercise.

Additional work to be reported at Experimental Biology looks at another characteristic of PPARd: its role as a major regulator of inflammation. Coronary artery lesions or atherosclerosis are thought to be sites of inflammation.

Dr. Evans found that activation of PPARd suppresses the inflammatory response in the artery, dramatically slowing down lesion progression. Combining the results of this new study with the original "marathon mouse" findings suggests that PPARd drugs could be effective in controlling atherosclerosis by limiting inflammation and at the same time promoting improved physical performance.

Dr. Evans says he is very excited about the therapeutic possibilities related to activation of the PPARd gene. He believes athletes, especially marathon runners, naturally change their muscle fibers in the same way as seen in the genetically engineered mice, increasing levels of fat-burning muscle fibers and thus building a type of metabolic 'shield" that keeps them from gaining weight even when they are not exercising.

But athletes do it through long periods of intensive training, an approach unavailable to patients whose weight or medical problems prevent them from exercise. Dr. Evans believes activating the PPARd pathway with drugs (one such experimental drug already is in development to treat people with lipid metabolism) or genetic engineering would help enhance muscle strength, combat obesity, and protect against diabetes in these patients.

Link to site

3 Comments:

Anonymous Anonymous said...

Andy,

I'm studing de PPARd deeply and in my opinion, we have a model case of the futur dopping:something between Gene and Biochemical Dopping.

The transcription control/regulation(trans, cis, activating factors, nuclear steroids, etc)seems to me, the really targets of the futur doping, and can we solve all this only with microarrays technology?
Or have we change the rules and create a medical structure, that follows the athlete all the way, before and after the games, based in his physiology?


What is your true opinion about this?
http://www.humanite.fr/journal/2003-07-01/2003-07-01-374933

A)Spicily pharmaceutic research?
B)A portrait of the society we have got?

Kind regards,
M (Biochemist)

1:03 pm  
Anonymous Anonymous said...

Sorry, I meant doping not dopping.
M

1:18 pm  
Blogger andymiah said...

Hi, I have not had a chance to see your article (french is not my strong point). However, the work from the Salk Institute is something I have thought a lot about. I think there are a number of things I should say on this matter. The first is to implore you to work with anti-doping agencies, specifically WADA, but not just to help them reach their ends. Actually, I think scientists could play a very important role in limiting the authority of sporting institutions and how they decide what kind of technology should be used by athletes. Certainly, it is widely recognised that there is not enough cooperation from non-scientists on these matters, though I fear that it is difficult to quash the anti-doping ethics. More likely, scientists will be broad in simply to support the philosophical commitment to eradicating doping from sport.


Yet, you indicate some reservations about the value of this project, which I think are crucial to explore. You will know very well that the prospects of detection are limited - even if we can detect some modifications, we cannot detect all.

We should also be concerned about the harmful effects of prohibition - underground science and drug mafias.

I do not think that gene doping jeopardises the contribution an athlete makes to society through their performance. It is imperative that a responsible ethical view is developed on this technology. Genetic scientists are not out of control, they are not aiming to create superhumans or mutants and, even the application of their work to sport, need not imply such negative connotations that are assumed.

One of the big difficulties, however, is that the liberal ethical view can easily be appropriated by big biotechnological companies whose aim is to capitalise on the widespread use of their technology, and we must be vigil to this.

Andy

3:17 pm  

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