The new workout plan: a pill? Researchers find molecule that cuts fat in obese mice after exercise

Mice on treadmills, the effect of exercise potentially placed in a pill—one new study has both.

The study comes from researchers at Baylor College of Medicine, Stanford School of Medicine and collaborating institutions. The team studied a molecule dubbed Lac-Phe, which is formed in the blood during exercise, discovering that it can suppress appetite and reduce obesity in certain mice, according to research published today in Nature.

Though physical activity is known to prevent obesity and obesity-associated diseases, some of the longer-term benefits of exercise on metabolic and physiological health are still unclear.

“We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits,” study co-author Jonathan Long, M.D., assistant professor of pathology at Stanford Medicine and an Institute Scholar of Stanford Chemistry, Engineering & Medicine for Human Health, said in a June 15 release. “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.”

The researchers analyzed blood plasma in mice after they completed intense treadmill runs and discovered the most significantly induced metabolite was Lac-Phe, which is synthesized from lactate (which creates an exercise-induced "muscle burn") and phenylalanine (a building block for proteins).

When obese mice on a high-fat diet were given a high dose of Lac-Phe, their food intake decreased by 50% over 12 hours, compared to control mice. The movement and energy spent in these mice was unaffected.

Over a 10-day period, the mice given Lac-Phe had a lower overall food intake, causing them to lose fat while also improving glucose tolerance.

Interestingly, Lac-Phe only suppressed appetite after exercise—not in the sedentary state—and was reported only in the obese mice fed a high-fat diet.

The research team also discovered that mice without CNDP2—an enzyme involved in the production of Lac-Phe—didn’t lose as much weight on an exercise regime when compared to a control group on the same workout plan.

Significant increases in Lac-Phe after physical activity, and subsequent drops in food consumption, were also observed in racehorses and humans. The findings indicate that Lac-Phe is an ancient and conserved system for eating regulation and is tied to physical activity in many animal species, Long said. For humans, sprinting induced the highest rise in Lac-Phe, followed by resistance training and then endurance training.

Further studies are required to better understand the downstream pathways of Lac-Phe action and the benefits of physical activity for humans, the authors concluded.