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A Workout for Your Bloodstream

What does exercise do to your body? It may seem as if science, medicine and common sense answered that question long ago. But in fact, the precise mechanisms by which exercise alters your body — at a deep, molecular level — remain poorly understood. A number of analyses of the effect that exercise has on heart disease, for instance, have concluded that working out lessens a person’s chances of developing heart problems far more than scientists can account for. They understand the physiological reasons for about 60 percent of the reduced risk. The rest is a mysterious if welcome bonus.

But a new study that gauged the metabolic effects of exercise may significantly advance our understanding of what’s going on inside a body in motion. During the experiment, scientists actually saw how much being fit changes your ability to incinerate fat, moderate blood sugar and otherwise function well. They also uncovered proof, at once inspiring and cautionary, of just how complicated and pervasive exercise’s consequences are.

In the experiment, published late last month in Science Translational Medicine, researchers from Harvard University and other institutions relied on a mass spectrometer to enumerate specific molecules in the bloodstreams of people who’d been exercising. The molecules were metabolites, which drive or are the byproduct of metabolic changes in the body. Metabolism is, of course, the chemical process of keeping yourself alive. All of the biochemical processes that feed and nurture cells constitute your metabolism. What the researchers wanted to know is, how does your metabolism change during and after exercise?

For the work, the scientists drew blood from a group of normal, healthy adults, as well as from a separate group who’d been referred for exercise testing because of shortness of breath or suspected coronary-artery disease. This group was relatively unfit. Each of the groups was told to exercise for about 10 minutes on a treadmill or a stationary bicycle, then had more blood drawn. Finally, the scientists also examined blood samples from a group of runners who had finished the 2006 Boston Marathon.

What they found was that after 10 minutes of treadmill jogging or stationary-bicycle riding, the healthy adults showed enormous changes in the metabolites within their bloodstream, as did the less-fit group, although to a lesser degree. In particular, certain metabolites associated with fat burning were elevated. The fit adults showed increases of almost 100 percent in many of these molecules. The less-fit group had increases in those same metabolites of about 50 percent. As for the marathoners, their blood contained up to 10 times more of the fat-burning markers.

These findings suggest that exercise has both “acute and cumulative” effects on your body’s ability to use and burn fat, says Gregory Lewis, a cardiologist at Massachusetts General Hospital in Boston and an author of the study. After only 10 minutes of exercise, even the least fit showed evidence that their bodies were burning fat; the more fit, the more metabolic evidence of fat burning.

The researchers then took a number of the metabolites that had been elevated by exercise and infused them into mouse muscle cells in a laboratory dish. Almost immediately, the metabolites, in combination (but not individually) ignited a reaction that resulted in increased expression of a gene involved in cholesterol and blood-sugar regulation. In other words, the metabolites weren’t just marking activity that was happening elsewhere in the body; they also may have been sparking some of that activity directly.

“That was exciting to see,” says Robert Gerszten, the director of clinical and translational research for the heart center at Massachusetts General Hospital and another author of the study. The result implies that exercise has complicated, chain-reaction metabolic effects; activity causes actions within cells that release metabolites, which, in turn, act on genes in ways that change your blood levels of fatty acids and blood sugar. These levels of fatty acids and blood sugar then play a role in your risks for heart disease, diabetes and other conditions.

Dr. Lewis cautions that his group’s work is still preliminary. “This is just a chemical snapshot,” static and limited, of a person’s bloodstream after exercise, he says. Even with mass spectrometry, not every type of metabolite can be captured, and the role of some of the metabolites that were uncovered remains unknown. But the experiment does reinforce the lesson, which we all know whether we heed it or not, that the human body needs to move.




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