New molecule as possible link between sports and lower food consumption

Researchers have discovered a molecule that might prevent obesity by suppressing food intake. The molecule, Lac-Phe, is produced in our bodies from lactate and is naturally released during physical exercise. In mice, the presence of the substance was revealed to play a role in the potential development of obesity. The study, led by researchers at Stanford University, will be published in Nature on June 15.

“Years ago, we discovered this molecule by chance, and at the time, we had no idea of its function”, explains co-author Robert Jansen of Radboud University. “It now seems like the molecule contributes to the positive effects of exercise on the body.”

Exercise leads to increased levels

About ten years ago, Jansen, together with amongst others Koen van de Wetering of Thomas Jefferson University, first discovered the molecule N-lactoyl-phenylalanine (Lac-Phe) in humans. “We were conducting research into proteins that pump molecules out of our cells; fundamental research that we carried out in the research group of Piet Borst at the Netherlands Cancer Institute. It had nothing to do with obesity.”

Lac-Phe is produced from lactate, which is synthesised during heavy exercise. Jansen’s research had already shown increased levels of Lac-Phe in the blood of people who had just taken a run. The researchers at Stanford University, who are interested in the effects of physical exercise on the substances in our blood, have now discovered that this increase in Lac-Phe levels is one of the most prominent changes in the blood of active mice, race horses and humans. Thanks to the earlier work done by Jansen and his colleagues, the American researchers were able to further explore what role Lac-Phe plays in the health benefits of sports.

Eat less

The researchers fed the mice a high-fat diet, which led to obesity. When the mice were administered Lac-Phe on a daily basis, however, the mice lost fat by the day and had shed 7% of their body mass after ten days. Their activity had remained the same, but they ate less. Mice that produced less of this substance due to a genetic mutation (called knock-out mice) benefitted less from daily exercise, when also given a high-fat diet. Every day, these mice ate a bit more than usual, and after 40 days, they were 13% heavier than the regular mice.

“There are still many unanswered questions regarding the exact function of the molecule”, Jansen says. “For example, we don't know how it affects the mice’s brain and leads to lower food consumption.” Similarly, the function of the substance on humans is not yet known. “Large studies in humans previously hinted that Lac-Phe could reduce obesity, but whether administering additional amounts of the substance will have the same effect in humans as it had in mice remains the question”, Jansen concludes.

Literature reference

Publicaties:

‘An exercise-inducible signaling metabolite that suppresses obesity’, Veronica L. Li et al., Nature. DOI: 10.1038/s41586-022-04828-5

‘N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids’, Robert Jansen et al., PNAS. DOI: 10.1073/pnas.1424638112

Contact information

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Organizational unit
Ecological Microbiology
Theme
Molecules and materials, Health & Healthcare