‘Exercise pill’ switches on gene that tells cells to burn fat

By giving ordinary adult mice a drug – a synthetic designed to mimic fat – Salk Institute scientist Dr. Ronald M. Evans is now able to chemically switch on PPAR-d, the master regulator that controls the ability of cells to burn fat. Even when the mice are not active, turning on the chemical switch activates the same fat-burning process that occurs during exercise. The resulting shift in energy balance (calories in, calories burned) makes the mice resistant to weight gain on a high fat diet.

The hope, Dr. Evans told scientists attending Experimental Biology 2007 in Washington, DC, is that such metabolic trickery will lead to a new approach to new treatment and prevention of human metabolic syndrome. Sometimes called syndrome X, this consists of obesity and the often dire health consequences of obesity: high blood pressure, high levels of fat in the blood, heart disease, and resistance to insulin and diabetes.

Dr. Evan’s Experimental Biology presentation on April 30 is part of the scientific program of the American Society for Biochemistry and Molecular Biology.

This chemical switch is not the first success Dr. Evan’s laboratory has had in being able to turn on the PPAR-d switch in adipose or fat cells, activating local metabolism and increasing the amount of calories burned. As a Howard Hughes Medical Investigator at The Salk Institute’s Gene Expression Laboratory, Dr. Evans discovered the role of the gene for PPAR-d, the master regulator of fat metabolism. By permanently turning on this delta switch in mice through genetic engineering, he was able to create a mouse with an innate resistance to weight gain and twice the physical endurance of normal mice. Because they were able to run an hour longer than a normal mouse, they were dubbed “marathon mice.”

Subsequent work in the Evans laboratory found that activation of PPAR-d in these mice also suppresses the inflammatory response associated with arthrosclerosis.

But the genetic metabolic engineering that created the marathon mouse is permanent, turned on before birth. While a dramatic proof of concept that metabolic engineering is a potentially viable approach, it offers no help to an adult whose muscles are already formed and who now would benefit greatly from having more active, fat-burning muscles.

That is why the potential of chemical metabolic engineering – possibly a one-a-day pill as opposed to permanent genetic metabolic engineering – is so exciting, says Dr. Evans. In today’s society, too few people get an ideal amount of exercise, some because of medical problems or excess weight that makes exercise difficult. Having access to an “exercise pill” would improve the quality of muscles, since muscles like to be exercised, and increase the burning of energy or excess fat in the body. And that would result in less fatty tissue, lower amounts of fat circulating in the blood, lower blood glucose levels and less resistance to insulin, lowering the risks of heart disease and diabetes.

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The ability to chemically engineer changes in metabolism also has given the researchers more insight into how the PPAR-d switch works, says Dr. Evans. Genetically engineering changes in metabolism in the marathon mice triggers both increased fat burning and increased endurance. Adult normal mice that receive the drug to switch on PPAR-d show increased fat burning and resistance to weight gain, but they do not show increased endurance. Dr. Evans says this suggests the delta switch can operate in different modes, and the laboratory is in the process of figuring out exactly how. He hopes his strategy will make it possible.

Source: Federation of American Societies for Experimental Biology

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37 thoughts on “‘Exercise pill’ switches on gene that tells cells to burn fat

  1. Suma

    Awesome. How soon can I expect to be sitting on my couch watching TV while at the same time burning off insane amounts of fat.

    Seriously, this rocks!

  2. Interesting. As you point out, it doesn’t have all the benefits of exercise (no increased endurance, no cardiovascular improvements, etc) but I think we’re all familiar with people who say they’re “too heavy” to work out. This could get them at least to a weight where they can’t claim that anymore.

  3. My concern is what happens when people with eating disorders get ahold of the pill, thus further shortening their life expectancy.

    How does the pill “know” when to stop?

  4. This is incredible, however another potential problem is that it doesn’t matter how thin you are it doesn’t make you healthy. i weigh 15 pounds above where i should be apparantly but i have broad shoulders and am overall a big person, completely capable of competing in sports, lol i sound bitter or something… what i’m trying to say is that this pill doesn’t make you healthy, it just makes you look better. Its like your body’s Listerine, but you still need to brush your body.. or exercise your teeth, oh whatever!

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  7. mai

    Very interesting article… This could be helpful for people like me who have a metabolism that doesn’t burn enough calories, even withregular exercise and healthy eating. Of course, it would have to be closely followed by a physician and not given to the wrong people. But there will always be people who use medical substances for the wrong reasons, this time it shouldn’t be any different. I don’t think it’s a good enough reason to stop people who could really benefit from it. But we’re not there yet anyway…

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  9. Extremely interesting. Like ANY developing drug though, its going to have its side effects, warnings, and sadly abusers. None the less its a great discovery that seemingly could lead into even bigger discovers.

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  11. Adrian

    Somehow I don’t think the weight loss will motivate obese people to exercise more, I think this is a behavioural issue, not a matter of physical ability. I abhor exercising and have been able to validate a ‘lazy day’ many times over. This ‘Exercise Pill,’ which is a misnomer, would likely encourage damaging diet and exercise habits.

    Why not eat pizza every day when there are no physically apparent consequences? It can probably promise a healthier-looking figure, but can it promise a healthy heart? Or liver?

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  14. This does sound exciting for those who REALLY need some help and are very obese or unable to
    do much. I , too, just hope it isn’t abused by those who might be lazy or hate exercise.
    I am a personal health consultant, and have worked as an aerobics instructor, and personal trainer for 30 years. To my knowledge NOTHING works as well as moving the human body…we
    are made to move. When I stop I’ll be dead:).

    Heaven forbid we stop building muscle, retaining bone mass and building endurance! Besides,
    anyone who exercises regularly KNOWS you create “feel good endorphins”.

    Interesting – thanks!

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  16. Hey, once you create such a drug, you won’t be able to avoid such abuse!

    So the best idea seems to not develop it into a medicament at all.

    I feel sorry for the people with symptom x, but that’s the only way to avoid that this substance is going to turn into the next cat walk and proana drug.

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  19. I am all old fashioned about exercise. But even if the ‘exercise pill’ really work as expected, I think that we still have a need to move our muscles. It is just part of the code in the gene, that human body is designed and built to move to maintain its mass and strength.

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  21. Leilani

    Ok I have read enough. It is about time. When is available, how soon can I get some and where do I go to order some….The soone the better

  22. peter

    The hype about this exercise pill shows a sorry state of affairs for our society. No one compound or “pill” can ever duplicate all the positive changes that occur in the body with exercise. Exercise turns on about 1000 genes and this article by Evans used only two products (GW and AICAR)which are similar to natural gene products(PPARd and AMPK). Note that there not one shred of evidence that the increased endurance ability of the mice had any health benefit. No health benefits were tested and yet the paper is being interpreted as leading to health as a substitute for exercise. Pure hype and pure nonsense.

  23. Very interesting article. I can attest that when when I was younger, losing weight was a breeze. I’d go on a low carb diet and drop a pound a day! Now I’m lucky if I drop a pound a month 😦

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