Mouse study reveals intense exercise could suppress your appetite

Researchers found a blood molecule that has been demonstrated to lower food intake after exercise in mice, racehorses, and people, as well as to cause weight reduction in obese animals.

The findings of a new study published in the journal Nature by researchers from Baylor College of Medicine, Stanford School of Medicine, and other institutions contribute to our understanding of the physiological processes that drive the exercise-hunger connection.

“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 co-corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor. “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 co-corresponding author Jonathan Long, MD, assistant professor of pathology at Stanford Medicine and an Institute Scholar of Stanford ChEM-H (Chemistry, Engineering & Medicine for Human Health). “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 performed in-depth investigations of blood plasma components from mice after severe treadmill jogging. The most strongly stimulated molecule was Lac-Phe, a modified amino acid. It is made from lactate (a result of hard activity that causes a burning feeling in the muscles) and phenylalanine (an amino acid that is one of the building blocks of proteins).

A high dosage of Lac-Phe decreased food intake by around 50% in mice with diet-induced obesity (given a high-fat diet) during a 12-hour period without influencing activity or energy expenditure. Lac-Phe decreased cumulative food intake and body weight (due to fat loss) in mice after 10 days of administration and enhanced glucose tolerance.

The researchers also discovered an enzyme called CNDP2 that is involved in the formation of Lac-Phe and demonstrated that mice missing this enzyme did not shed as much weight on the same exercise regimen as a control group.

Interestingly, the team also found robust elevations in plasma Lac-Phe levels following physical activity in racehorses and humans. Data from a human exercise cohort showed that 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,” Long said.

“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.”

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