NIH Record - National Institutes of Health

New Clue into How Exercise Influences Body Weight

An overweight man in blue shirt jogs near office building.
A molecule that increases with exercise suppressed appetite in mice.

Physical activity leads to many molecular changes in the body, but it remains unclear how exercise protects against obesity at a molecular level.

A team of researchers led by Drs. Yong Xu at Baylor College of Medicine and Jonathan Long at Stanford University analyzed blood samples taken from mice before and after intense running on a treadmill. The scientists looked for compounds in blood plasma with higher levels after exercise. The study, partly funded by NIH, appeared in Nature.

The team found that the largest exercise-induced increase was in a compound called N-lactoyl-phenylalanine, or Lac-Phe. The team found a similar increase in Lac-Phe after exercise in blood samples from thoroughbred racehorses. They also analyzed blood samples from people and found increases in Lac-Phe after various types of exercise. These findings suggest that the exercise-induced increase in Lac-Phe likely occurs across mammals.

When mice were fed a high-fat diet, injecting a large dose of Lac-Phe reduced food intake by about half over 12 hours even though blood Lac-Phe levels fell back to baseline level within an hour. Lac-Phe treatment did not affect the mice’s movement or energy expenditure. Obese mice treated with Lac-Phe daily for 10 days lost weight compared to control mice. This was due to a decrease in body fat. Obese mice treated with Lac-Phe also had lower blood glucose levels than control mice. Lac-Phe treatment, in contrast, did not affect food intake in lean mice eating a normal chow diet.

“Regular exercise has been proven to help weight maintenance, regulate appetite and improve the metabolic profile, especially for people who are overweight and obese,” Xu said. “If we can understand the mechanism by which exercise triggers these benefits, then we are closer to helping many people improve their health.”

“Our next step,” said Long, “is to identify the brain Lac-Phe receptor in order to understand how Lac-Phe suppresses feeding and obesity.”—adapted from NIH Research Matters

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