Mass. General scientists discover molecule that may underlie benefits of exercise

A November Project group works out at Harvard Stadium.
Dozens of hardy souls ran the Harvard Stadium steps on Christmas Morning at 6:30am. They are part of The November Project, a fitness group –Dina Rudick/Globe Staff

Everyone knows exercise is good for you: it’s a good way to prevent practically all the diseases that come with age, stave off weight gain, and even relieve anxiety. But how does it work? What is the set of molecular events triggered by a session at the gym or a morning jog that results in what we recognize as good health?

For years, researchers have been slowly untangling exercise at the cellular level — if they can figure that out, they think it might be possible to emulate the beneficial effects of a workout with a pill. Now, a team led by researchers at Massachusetts General Hospital has identified a molecule that might be responsible for some of exercise’s beneficial effects.


The researchers are still far from creating exercise in a capsule, but the early work published Tuesday in the journal Cell Metabolism has produced an intriguing clue. The small molecule, generated by muscles during exercise, helps convert normal energy-storing white fat to become energy-burning brown fat and improves blood sugar levels in mice.

The work builds off the discovery two years ago, by researchers at Dana-Farber Cancer Institute, of a previously unknown hormone that induces changes to fat that cause it to burn energy in mice. In the new work, that group collaborated with researchers at Mass. General to search for smaller molecules that are secreted by muscles that might have similar effects. When they saw a compound called BAIBA, short for beta-aminoisobutyric acid, pop out in their screening test, they were instantly intrigued.

Dr. Robert Gerszten, director of clinical and translational research at the Massachusetts General Hospital Institute for Heart, Vascular and Stroke Care, said that what excited the team was that this molecule had been seen in very different samples from their laboratory tests. In samples taken from participants in the long-running Framingham Heart Study, levels of BAIBA were high when measures of heart health were high, and vice versa.


“We said, ‘BAIBA, I remember that one,’ ’’ Gerszten said. “The more BAIBA, the lower your insulin, the better your glucose, the less you weigh.’’

That was what hooked the researcher’s interest, but it was just a correlation. So the researchers did detailed studies of the molecule’s mechanism in cells in a dish and in live animals and found that it turned white fat into energy-burning brown fat. In mice, increased levels of BAIBA resulted in a slight decrease in weight, decreased body fat, increased energy expenditure, and improved blood sugar. Then, in another study of people on an exercise program, they found that BAIBA levels increased after a 20-week exercise program.

Gerszten is quick to note that the research is still early: they have much to learn about how BAIBA has its effects, and to explore what other compounds might be involved in the signaling. He hopes to eventually move toward testing BAIBA in humans or developing a therapy based on the insights.

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