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Could the benefits of exercise be packaged in a pill?

Regular exercise is known to have many health benefits, including increased metabolic rate, weight loss and regulation of appetite. These are important effects, particularly for people who are overweight or obese. But we all know that exercise is hard work and that it can have negative effects on joint health. Some elderly people, as well as those with injuries, may not be able to exercise, despite the desirable effects. 

Wouldn’t it be nice if we could simply take a pill and experience these benefits of exercise? Scientists say that they are actually getting closer to this goal.

A team of researchers led by Baylor College of Medicine has identified a molecule in the blood of mice that is produced during exercise and can effectively reduce food intake and obesity in these animals. This molecule was also identified in the blood of race horses and humans, and could help clarify the relationship between exercise and its effects on the regulation of appetite and weight..

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

“We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits,” said Dr. Jonathon Long. “For example, older or frail people who cannot exercise enough, may one day benefit from taking a medication that can help slow down osteoporosis, heart disease or other conditions.”

Xu, Long and their colleagues analyzed blood plasma compounds from mice that had exercised intensively by running on a treadmill, and compared these to plasma compounds in mice that had not exercised. The most notable molecular difference was the levels of a modified amino acid called Lac-Phe in the blood of mice that had exercised. Lac-Phe is synthesized from lactate (a byproduct of strenuous exercise that is responsible for the burning sensation in stiff muscles) and phenylalanine (an amino acid that is one of the building blocks of proteins).

When obese mice received a high dose of Lac-Phe over a period of 12 hours, their food intake was suppressed by about 50 percent in comparison to control mice. When this high dose was administered to the obese mice over 10 days, their cumulative food intake decreased, they lost weight and showed improved glucose tolerance. 

The researchers also identified an enzyme called CNDP2 that is involved in the production of Lac-Phe, and showed that mice that lacked this enzyme did not lose as much weight on an exercise regime as a control group on the same exercise plan.

Furthermore, the experts found increased levels of Lac-Phe in the blood plasma of race horses and humans, after strenuous exercise. In a human cohort, sprint exercise induced the most dramatic increase in plasma Lac-Phe, followed by resistance training and then endurance training. 

“This suggests that Lac-Phe is an ancient and conserved system that regulates feeding and is associated with physical activity in many animal species,” said Long.

“Our next steps include finding more details about how Lac-Phe mediates its effects in the body, including the brain,” Xu said. “Our goal is to learn to modulate this exercise pathway for therapeutic interventions.”

The study is published today in the journal Nature.

By Alison Bosman, Staff Writer

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