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Study breaks down how exercise builds you up

Researchers probe molecular changes in local athletes

By Carolyn Y. Johnson
Globe Staff / May 27, 2010

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Everyone knows exercise can be good for body and mind. But even as doctors admonish young and old to get off the couch to stave off such diseases as diabetes and dementia, they cannot explain how exercise works.

Now, a team of local researchers has begun to unravel the secrets of exercise, in part by analyzing blood samples taken minutes after runners crossed the Boston Marathon finish line. The findings, they say, could begin to reveal how exercise achieves its potent effects and could lead to ways of improving athletic performance or treating disease.

“What other medicine can you think of that would be associated with living longer, better brain function, better cardiovascular function, better blood vessel function, less depression?’’ said Dr. Gregory Lewis, a cardiologist at Massachusetts General Hospital and lead author of the study published yesterday in the journal Science Translational Medicine. “It’s basically like the ultimate intervention. Our large-scale objective is to try and unlock some of the mystery behind why exercise has such beneficial effects.’’

The scientists used new tools to take chemical snapshots of what is going on in the bodies of people before and after they exercised, whether running the streets of Boston or riding an exercise bike. They found that exercise affects fit people differently than those who are less fit, and they identified 21 molecules in the bloodstream, called metabolites, that respond to exercise.

Understanding how exercise works at the molecular level could ultimately give scientists clues about how to design training regimens or nutritional supplements. By knowing how exercise works biologically, researchers could begin to find treatments that can emulate its beneficial effects for people with cardiovascular disease or to help couch potatoes get the same bodily boost from exercise as marathoners.

Their starting place in this ambitious quest are 21 metabolites that are like signposts indicating how exercise causes fat, sugar, and carbohydrate to be used as fuel. They are involved in activities such as controlling insulin levels and cellular stress.

“We know that exercise is good for you; the question is why it is good for you, and this paper is a start of understanding this a little bit more,’’ said Dr. Charles Burant, professor of internal medicine at the University of Michigan Medical School, who was not involved in the research. “They really show the power of the [new] technology to be able to provide a new window into metabolism related to exercise.’’

Scientists took blood samples from people before, after, and sometimes during exercise. In the days before the 2006 Boston Marathon, 25 runners came to Mass. General or to a downtown hotel room to have baseline samples taken. Minutes after they finished the race, they reported to a nearby tent.

Dr. Tomas Neilan, an MGH cardiologist, had his blood drawn after finishing the marathon in about 3 hours, 25 minutes. “The one thing I’ll say after you run 26.2 miles,’’ Neilan said. “It’s kind of nice to lie down.’’

Scientists also took samples from eight people who rode exercise bikes with catheters placed in blood vessels near their heart. Another 70 subjects had blood taken before, after, and at their peak while running on a treadmill.

Then, cutting-edge tools developed in collaboration with researchers at the Broad Institute, a genetics research center in Cambridge, measured changes in 200 metabolites. By finding metabolites affected by exercise, scientists gleaned clues about how it affects different people.

The researchers found that glycerol, a metabolite released into the bloodstream when fat is burned, increases during exercise, with levels twice as high in fit people than in those less fit. Niacinamide, a metabolite involved in regulating insulin levels, increased more in lean people.

“One of the questions that rises from that is does that mean that people are born to be more fit or more athletic or more lean? . . . Or is it because they go to the gym three times a week and they’ve had this training-based effect that their body is a better fat-burning machine?’’ said Lewis, who became interested in studying the physiological effects of exercise when he took a year off from medical school to train for the 1996 Olympic rowing team and participated in medical studies.

A future research question will be to understand whether becoming more fit may change the metabolic effects of exercise.

Debbie Muoio, associate professor at the Sarah W. Stedman Nutrition and Metabolism Center at Duke University Medical Center, said the new results show in part how difficult it would be to mimic in a drug the range of effects exercise has on the body.

At the same time, she said, the new tools are a step toward better diagnosing cardiovascular or diabetes risk or finding ways to help people exercise in the way most effective for their body.

“The studies to date are really what we like to think of [as] the first comprehensive chemical snapshot of exercise,’’ said Dr. Robert Gerszten, senior author of the paper and director of clinical and translational research for the MGH Heart Center.

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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