If this works, this guy is going to make a bagillion dollars:
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. (Emphasis mine.)
I have to say that I am a tad skeptical that this is going to work without side effects. True, the signaling cascades activated by exercise are just that -- signaling cascades. Exercise works because it changes the molecular biology of cells, and there is no reason that we can't enforce that same type of activation sans all the running around.
However, fiddling with metabolic regulation can all have unfortunate consequences, not the least of which are the production of oxygen radicals and the possibility of cancer. I like the way this guy is thinking, but I am really curious to see what other things are going to happen to these mice.
If it does work, however, we could start putting this drug in the water and create a race of superhot, lazy people. That would be awesome, because I am tired of getting my lame ass out of bed to go running in the morning. I would really to have my exercise administered with my breakfast cereal in front of CNN rather than in the Park in the freezing rain.
Incidentally, the paper where the Evans lab showed the marathon mice is available from PLoS Bio here. It is discussed in this news article here.
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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
Jake:If it does work, however, we could start putting this drug in the water and create a race of superhot, lazy people
The first human use of such a drug is likely to be some smuggled out of the lab for endurnce athletes. Looks far better than blood doping/rEPO. Putting it in the water would make everyone who had access to the water supply a better athlete, but this obviously would not be universally available. The Olympic doping agency would have a lot to say about the fairness of this.
Some thoughts in no particular order:
* So this isn't a way to prevent someone getting fat, rather a treatment. But what happens to the energy released when the fat is burned?
* What happens when there's no fat to burn? Presumably the body will move on to other tissue types, including muscle. A whole new way to become anorexic.
* Does the drug work better when combined with exercise? I mean, is a small dose plus exercise more effective than a large dose without?
* Some health-conscious but stupid parent is going to give this stuff to children. Maybe very young children. Pregnant women might take it to stay slim. What are the likely effects?
Shoot, I'd settle for a pill that actually helped me stop eating so much. There's no real cure for compulsive eating and binge eating disorder.
* So this isn't a way to prevent someone getting fat, rather a treatment. But what happens to the energy released when the fat is burned?
Actually it could do both - treating overfat and preventing it. As for the excess heat produced, I would imagine that standard thermoregulatory mechanisms would take over - vasodilation of surface vascular beds, increased sweating, etc. One side effect would be greater cold tolerance with greater heat intolerance and need for increased fluid intake.
* What happens when there's no fat to burn? Presumably the body will move on to other tissue types, including muscle. A whole new way to become anorexic.
Likely to be correct. I would imagine that when there is little body fat, the normal adaptations to starvation would take over. For weight maintenance, an increase in caloric intake would be necessary.
* Does the drug work better when combined with exercise? I mean, is a small dose plus exercise more effective than a large dose without?
The most interesting question about the drug. Is there a Vmax for mitochondrial biogenesis for exercise alone? would it change if exercise and the drug were combined? Would someone [or lots of people] be able to do a sub 2 hour marathon? I would imagine that if there is a maximal amount of stimulation of mito biogenesis, there would still be enough individual variability to produce clear endurance champioons. There would probably just be a few more people in the elite category because one would probably need to train less to achieve one's maximum capabilty, reducing overuse injuries that are a major factor in reducing the number of elite athletes. All speculation, of course.
What a GREAT idea for permanently disabled people who cannot do physical activity!