Is there a molecular reason you don’t feel hungry after exercise?

If you’ve ever found yourself surprisingly unhungry after a strenuous workout, a team of researchers at multiple institutions may have the molecular explanation. The peptide N-lactoyl-phenylalanine (Lac-Phe), which is produced during exercise from the enzymatic condensation of lactate and phenylalanine, seems to suppress appetite, at least in mice (Nature 2022, DOI: 10.1038/s41586-022-04828-5).

In 2015, researchers discovered that levels of the metabolite Lac-Phe spike after exercise (Proc. Natl. Acad. Sci. U.S.A., DOI: 10.1073/pnas.1424638112), but Jonathan Long’s Stanford University lab wanted to measure all the exercise-induced metabolites. Using mass spectrometry, the researchers measured the levels of molecules in the blood of mice, racehorses, and humans and found that the amount of Lac-Phe rose the most after exercise. In addition, the workout’s intensity affected the size of the increase. For example, male volunteers who did cycle sprints had more Lac-Phe in their blood than those who cycled at a leisurely pace.

The group spotted a link between Lac-Phe and hunger when it gave the molecule to obese mice and found that they lost interest in their food. Those mice ate about 30% less food and lost weight over time.

It may seem counterintuitive to not be hungry after exercise, when you might want to replenish energy stores. But the types of strenuous activities the researchers studied may act as a proxy for external stress, says Scott Sternson, who studies the neurobiology of survival needs like hunger at the University of California San Diego and was not involved in the study. For example, he notes, it is better not to be distracted by hunger if you are trying to run away from a predator. Sternson cowrote a commentary about the study (Nature 2022, DOI: 10.1038/d41586-022-01321-x).

Researchers still don’t understand how Lac-Phe suppresses appetite or why exercise reduces appetite in some people but not in others. Studying differences in levels of the metabolite and its signaling in different people could help researchers understand the variation in the effectiveness of exercise as an approach to weight loss, Sternson says.