Exercise has long been praised as one of the best ways to lose weight and stay healthy, but scientists are still uncovering exactly how it works.
Beyond simply burning calories, new research shows that exercise triggers a natural compound in the body that helps reduce appetite.
The study, published in Nature Metabolism, focuses on a molecule called Lac-Phe.
This compound is produced in large amounts after intense exercise, not only in mice but also in humans and even racehorses.
Researchers have known that giving Lac-Phe to obese mice made them eat less and lose weight, without harmful side effects. But until now, they didn’t fully understand how Lac-Phe actually suppresses hunger.
Dr. Yang He, assistant professor at Baylor College of Medicine and one of the study’s senior authors, explained: “Exercise helps with weight loss by increasing the energy the body burns. But we believed other mechanisms were also at play.”
To find answers, the team studied the brains of mice, focusing on two groups of neurons—specialized brain cells that control appetite. One group, called AgRP neurons, stimulates hunger and makes you want to eat.
The other group, PVH neurons, does the opposite: it helps suppress hunger and signals that you’re full.
Under normal conditions, AgRP neurons send strong signals that block PVH neurons, which makes you feel hungry. But Lac-Phe appears to shift this balance. The researchers discovered that Lac-Phe directly shuts down AgRP neurons.
When these hunger-promoting neurons are silenced, PVH neurons become more active, reducing appetite. The mice ate less food, yet their overall behavior remained normal, showing that Lac-Phe’s effect didn’t cause discomfort or side effects.
The team also dug deeper into how Lac-Phe acts on AgRP neurons. They found that it works through a protein called the KATP channel, which helps regulate how active brain cells are.
When Lac-Phe activates this channel, AgRP neurons quiet down. But when the researchers blocked the KATP channel using drugs or genetic tools, Lac-Phe lost its ability to suppress appetite. This proved that the channel is essential for its effects.
“These findings help explain how exercise naturally reduces appetite,” said Dr. Yong Xu, co-corresponding author, now at the University of South Florida. “It also raises the exciting possibility of targeting this mechanism to help people manage weight.”
While the study was done in mice, the discovery is promising for humans. Scientists plan to explore how Lac-Phe behaves in different conditions, such as obesity versus leanness, and whether it could one day be safely developed into a treatment.
As Dr. Jonathan Long of Stanford University, another senior author, put it: “This shows how a molecule our bodies naturally produce during exercise can influence appetite by directly interacting with the brain’s hunger circuits.”
The research highlights an important point: exercise doesn’t just burn calories—it also changes the way our brains regulate hunger, offering a double advantage in the fight against obesity.
