Science News -- June 23, 2022: Researchers from Baylor College of Medicine, Stanford School of Medicine, and partner institutions have identified a chemical in the blood that is created during exercise

and can successfully lower food intake and obesity in mice. The findings were published today in the journal Nature. The findings enhance our knowledge of the physiological processes underlying the interaction between exercise and hunger.

"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."

Following vigorous treadmill jogging, Xu, Long, and their colleagues conducted exhaustive analysis of blood plasma components from mice. The most highly stimulated molecule was Lac-Phe, a modified amino acid. It is produced from lactate and phenylalanine. Lactate is a byproduct of intense exercise and is responsible for the burning sensation in muscles (an amino acid that is one of the building blocks of proteins).

A high dose of Lac-Phe decreased food intake by around 50 percent in mice with diet-induced obesity (given a high-fat diet) compared to control mice over a 12-hour period without changing their mobility or energy expenditure. Lac-Phe lowered cumulative food intake and body weight (due to loss of body fat) and enhanced glucose tolerance when provided to mice for 10 days.
The researchers also found an enzyme called CNDP2 that is involved in the generation of Lac-Phe and demonstrated that animals deficient in this enzyme did not lose as much weight during exercise as mice in the control group that followed the same exercise regimen.
Intriguingly, the scientists also discovered significant increases in plasma Lac-Phe concentrations following physical activity in both racehorses and people. Sprint activity generated the most dramatic increase in plasma Lac-Phe, followed by resistance training and then endurance training, according to data from a human exercise cohort.

"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."

Wnctimes by Marjorie Farrington

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Baylor College of Medicine. "The benefits of exercise in a pill? Science is closer to that goal." ScienceDaily. ScienceDaily, 15 June 2022. .