June 2, 2010 -- Small molecules in the blood not only reveal the "metabolic signature" of fitness, but hint at how new sports drinks or drugs might help people more effectively burn fat.
Using new technology, Massachusetts General Hospital researchers Gary Lewis, MD, Robert Gerszten, MD, and colleagues tracked more than 200 small molecules in the blood.
The molecules are the end products -- metabolites -- produced as the body goes about its business of converting sugars, fats, proteins, and amino acids into energy.
When Lewis's team looked at the metabolite profiles of relatively healthy, middle-aged, overweight men and women before and after a prescribed 10-minute exercise stress test, they got a surprise. Those who were more fit had a very different metabolite profile than those who were not fit, revealing a "metabolic signature" of fitness.
"People who are more fit are able to mobilize the fuel source in fat better than those who are less fit," Lewis tells WebMD. "That is a very interesting finding. Certain individuals will burn fat much more robustly than others."
That goes tenfold for marathon runners. When the researchers analyzed blood metabolites in 25 people who had just run the Boston Marathon, they found that they had gone into an intense fuel-burning mode that consumed fat a thousand times more effectively. Interestingly, those with above-average finish times had fewer harmful metabolites in their blood than those who finished with below-average times.
The increased ability to burn fat and other fuels, even in normal people, continued for at least an hour after they stopped exercising. And fat burning wasn't the only positive effect. Exercise also acted like an antioxidant, reducing oxidative stress in the body.
Opposite findings come from studies of sedentary people. Lewis says their metabolic profile indicates that their bodies get better and better at storing up fat reserves.
"With exercise you tap into all these fuels in the body and put yourself into a fuel-burning mode," Lewis says. "Unfortunately, the balance in a lot of people is tipped toward over-storage mode and away from this marked metabolic response seen in even a short bout of exercise."
Fitness in a Bottle?
It's not yet clear from the studies what it is that makes a person more fit.
"What we still are sorting out is, are these fit people inherently different based on genetics -- people who are meant to be lean and who when they walk across the street burn more fat? Or by going to the gym three times a week, have they been able to alter their metabolism to burn fat more robustly?"
A tantalizing hint comes from further studies suggesting that the metabolites seen after exercise aren't just by-products of fuel burning. They may play an active role in promoting fitness.
"When we exposed muscle cells to some of the metabolites that increase after exercise, we found they turned on an important gene that regulates the ability to use glucose [sugar] in fats," Lewis says. "So exercise through these small molecules that are released can stimulate expression of genes that are important to our metabolism."
Indeed, one gene activated by these exercise-associated molecules is nur77, a gene that helps control how the body burns or stores sugar and fat.
"If you look at a sports drink label, you'll see the drink contains handfuls of small molecules. But think of supplementing that drink with all these molecules we now know the body uses up during exercise," Lewis says. "So you can imagine we might be able to use these findings to craft the next generation of sports drinks."
And by studying the metabolic profiles of people with heart disease and other conditions, the researchers also hope to learn whether certain metabolites -- or drugs that mimic their action -- can be therapeutic.
But if all we want to do is lose weight, all the small molecules in the world might not be enough, cautions Andrew S. Greenberg, MD, director of the obesity and metabolism laboratory and the center on aging at Tufts University.
"Just because you have these metabolites does not mean that if you put them into your muscles you would be fit," Greenberg tells WebMD. "You don't just get on a treadmill and burn fat. It takes a long-term process of resetting the thermostat of how your body responds to exercise."
Exercise is just one part of the fitness equation, Greenberg says. Diet is the other.
But Joshua C. Munger, PhD, assistant professor of biochemistry and biophysics at Rochester University, notes that the Lewis study is breaking new ground in helping scientists understand the benefits of fitness.
"We understand that it is good for you to get plenty of exercise, but it is not clear exactly where the benefit lies," Munger tells WebMD. "The enticing question raised by the Lewis study is whether these metabolites could play a causal role in modulating the pathways leading to fitness."
The Lewis/Gerszten study appears in the May 26 online issue of Science Translational Medicine.