We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Appetite-Suppressing Molecule Could Be Why You Don’t Feel Hungry After a Hard Workout

Appetite-Suppressing Molecule Could Be Why You Don’t Feel Hungry After a Hard Workout

Appetite-Suppressing Molecule Could Be Why You Don’t Feel Hungry After a Hard Workout

Appetite-Suppressing Molecule Could Be Why You Don’t Feel Hungry After a Hard Workout

Read time:

Want a FREE PDF version of This News Story?

Complete the form below and we will email you a PDF version of "Appetite-Suppressing Molecule Could Be Why You Don’t Feel Hungry After a Hard Workout"

First Name*
Last Name*
Email Address*
Company Type*
Job Function*
Would you like to receive further email communication from Technology Networks?

Technology Networks Ltd. needs the contact information you provide to us to contact you about our products and services. You may unsubscribe from these communications at any time. For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out our Privacy Policy

A poorly-studied metabolite may play a role in suppressing appetite after an intense workout, finds a new study published in Nature. The research, mainly conducted in mice, also showed the molecule was boosted by intense exercise in racehorses and humans.

The health benefits of exercise

Exercise is something we all do (or at least consider doing before sitting back down on the sofa again). Exercise provides a long list of health benefits, such as improved cardiovascular performance, better regulation of blood sugar and reduced body fat. But the reasons why exercise confers such health benefits are surprisingly unclear.

The main route to answering this question is via untangling the complex metabolic pathways that exercise sets off. Researchers, led by senior author Jonathan Long, an assistant professor of pathology at Stanford University, set up an experiment that involved running mice on a treadmill until they became exhausted, before examining the molecules in their blood that increased or decreased in concentration after exercise. The authors initially examined levels of well-established exercise-linked molecules such as lactate – the chemical that makes your muscles ache after an intense workout – and fumarate.

These molecules were indeed boosted in the tired mice’s bodies, but the real surprise lay in a second analysis the team conducted. This was an untargeted approach, that didn’t look for pre-selected molecules, but was instead a broad sweep of all detectable metabolites. The molecule most highly expressed, topping even the well-known exercise-related metabolites, wasn’t anywhere on the team’s target list.

The team managed to ID the mystery molecule as Lac-Phe, a metabolite formed by a merger between lactate and an amino acid, phenylalanine. A separate experiment showed that Lac-Phe also topped the charts of molecules most strongly expressed after exhaustive exercise in racehorses.

The mysterious exercise molecule

Lac-Phe has previously been tied to exercise but is a poorly-studied molecule of unknown function. The team noted that mutations in an enzyme called CNDP2 that can produce Lac-Phe have been linked to changes in body mass. They proposed that the boost in Lac-Phe might have a role in regulating energy balance.

The team decided to look at the effects of injecting an above-average dose of Lac-Phe into obese mice that had been fed a high-fat diet. Despite Lac-Phe effectively leaving the body after an hour, the team noticed that for the 12 hours following injection, the normally ravenous rodents lost their appetite, cutting their food intake by 50%. This wasn’t due to the mice moving less, and a separate experiment showed that Lac-Phe didn’t affect the obese mice’s water consumption. The hunger-halting effects of Lac-Phe were only seen in mice hooked on a high-fat diet – mice given regular chow didn’t cut their food consumption.

They followed up this finding with a longer study, giving the mice Lac-Phe over a period of 10 days. This had the effect of cutting the obese mice’s food intake and body weight and improving their glucose balance and fat levels. They also showed that mice lacking the CNDP2 enzyme required to produce Lac-Phe showed higher appetite and body weight. This latter effect was only seen when the mice vigorously worked out, suggesting that Lac-Phe’s effects are largely exercise-dependent.

Which exercise induces Lac-Phe the most?

Using animal models as different as mice and racehorses make these initial findings more robust, but the authors wanted to see whether Lac-Phe levels followed a similar trend in humans. In a group of 36 people, they showed that Lac-Phe was the third-most highly expressed molecule post-exercise. When looking at different types of exercise, the researchers found that the Lac-Phe increase was most strongly induced by sprint training, followed by resistance and then endurance training.

There are still plenty of outstanding questions surrounding Lac-Phe. To alter appetite, the molecule must act on one of three types of neural circuit, each of which govern a different type of eating behavior. These are the energy-detecting homeostatic system that regulates normal body function, the satiety circuits that tell us when we are full and the appetite pathways that are motivated by reward.

In a companion article, Tahnbee Kim and Scott M. Sternson, of the Howard Hughes Medical Institute and the University of California, San Diego, suggest that the effect may be primarily on pleasure-driven eating. But the pathways that connect Lac-Phe, which appears to be produced in a range of cell types including immune and epithelial cells (these line our body’s external and internal structures) with the brain are currently unclear.

More questions surround what Sternson tells Technology Networks is the “main surprise from this study”: the finding that an exercise-dependent molecule can suppress hunger. Why doesn’t the tired-out body increase hunger to make up for lost calories? Kim and Sternson suggest that the intense exercise that the study’s participants were subjected to might be an explanation. “One possibility is that the type of strenuous exertion studied by Li and colleagues is indicative of a stressor that threatens immediate survival: energy intake is deprioritized because it is necessary only for longer-term survival. For example, it is better not to be distracted by hunger when trying to escape predators,” they write.

Long, writing to Technology Networks, offers another explanation: “We think the induction of Lac-Phe after exercise corresponds to the feeling of wanting to vomit after a hard workout. By contrast, light to moderate endurance exercises (like walking around the block) do not generate as much Lac-Phe.”

More research will definitely be required to confirm the findings – exercise research can often produce conflicting results. Part of that conflict relates to sex. Sternson notes that “mostly consistent” past reports suggest that exercise can suppress hunger in men. The results in women, he says, “are more variable.” As Long’s team only studied male mice, further work will be needed to work out how useful these findings might be for people wanting to use exercise to lose weight.

Long acknowledges the variability in the field’s wider conclusions, but stands behind his latest study. “We think Lac-Phe induction after intense exercise is why you don’t feel hungry after a hard workout.”


Reference: Li VL, He Y, Contrepois K et al. An exercise-inducible metabolite that suppresses feeding and obesity. Nature. 2022. doi: 10.1038/s41586-022-04828-5.

Meet the Author
Ruairi J Mackenzie
Ruairi J Mackenzie
Senior Science Writer