A conserved exercise-induced metabolite, identified in an animal trial, appears to help control food intake and modulate energy balance, potentially opening the path to delivering its effects in a supplemental way. Researchers from Baylor University, Stanford School of Medicine and collaborating institutions published their findings in Nature (ePub 15 June 2022; DOI:10.1038/s41586-022-04828-5).

Investigators conducted comprehensive analyses of blood plasma compounds from mice following intense treadmill running. Exercise stimulated the production of N-lactoyl-phenylalanine (Lac-Phe), a signalling metabolite that suppresses feeding and obesity. In mice with diet-induced obesity—fed a high-fat diet—a high dose of Lac-Phe suppressed food intake by about 50% compared to control mice over 12 hours without affecting energy expenditure. Chronic administration of Lac-Phe (over a 10 day period) decreased adiposity and body weight, and improved blood glucose levels.

“We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits,” said co-corresponding author Dr. Jonathan Long, assistant professor of pathology at Stanford Medicine and an Institute Scholar of Stanford ChEM-H (Chemistry, Engineering & Medicine for Human Health) in a statement. “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.”

In addition, blocking Lac-Phe biosynthesis in healthy mice increased food intake and obesity following exercise training. The mice that lacked the enzyme CNDP2, which is involved in production of Lac-Phe, did not lose as much weight as control mice on the same exercise plan. Researchers also noted previous research has shown robust elevations in plasma Lac-Phe levels following physical activity in humans and racehorses, suggesting the metabolite is associated with physical activity across multiple modalities and mammalian species.

“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, in the statement. “If we can understand the mechanism by which exercise triggers these benefits, then we are closer to helping many people improve their health.”