SAN FRANCISCO, October 7, 2025: A new study led by researchers from Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, and Stanford University School of Medicine has identified how a molecule produced during exercise can reduce appetite, offering new insight into the biological mechanisms behind weight loss. The research, published in Nature Metabolism, found that a compound known as N-lactoyl-phenylalanine, or Lac-Phe, generated during physical activity, directly impacts neurons in the brain that regulate hunger.
The study was conducted using mouse models and built on earlier work by the same team, which had previously demonstrated that Lac-Phe levels rise sharply in the bloodstream following intense exercise and that the molecule can reduce food intake in obese mice without adverse effects. In the latest study, scientists focused on two types of neurons located in the hypothalamus, the brain region that controls hunger. These include AgRP neurons, which promote the sensation of hunger, and PVH neurons, which suppress it. Under normal circumstances, AgRP neurons inhibit PVH neurons, increasing the drive to eat.
The researchers discovered that Lac-Phe acts directly on AgRP neurons, suppressing their activity and allowing PVH neurons to become more active, thereby reducing appetite. Dr. Yang He, assistant professor of pediatrics-neurology at Baylor College of Medicine and investigator at the Duncan NRI, said the team was able to identify the specific mechanism through which Lac-Phe influences appetite. The molecule activates a protein on AgRP neurons known as the KATP channel, which controls cellular activity. When this channel is activated, the AgRP neurons become less active, effectively lowering the sensation of hunger.
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To validate the mechanism, the team used pharmaceutical and genetic tools to block the KATP channels. When these channels were disabled, Lac-Phe no longer suppressed appetite in the mice, confirming the essential role of this protein in the pathway. Throughout the experiments, the mice maintained normal levels of physical activity and behavior, indicating that Lac-Phe’s effect on appetite did not come with other behavioral changes or disruptions. The researchers also tested the effects of Lac-Phe in different dietary settings. When administered to mice fed a high-fat diet, the molecule continued to reduce food intake, suggesting that the appetite-suppressing effects are not limited to a specific nutritional context.
Injections of Lac-Phe into the brain as well as the body cavity both led to similar outcomes, indicating the compound’s ability to influence central appetite regulation. Lac-Phe is a metabolite formed from lactate and phenylalanine during exercise. It had previously been observed to rise significantly in the bloodstream of not only mice but also in humans and racehorses after physical activity. While the current findings are limited to animal studies, the identified biological pathway offers a clear explanation of how exercise can suppress hunger beyond the commonly known energy expenditure mechanisms.
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The study was a collaborative effort involving multiple research institutions, including Baylor College of Medicine, Stanford University School of Medicine, the University of Copenhagen, and the University of Pennsylvania. Funding was provided by several U.S. federal agencies, including the National Institutes of Health and the Howard Hughes Medical Institute. Researchers emphasized that while the study offers important insight into the biology of exercise-induced appetite control, the findings are based on controlled laboratory conditions in mice.
Further research will be required to determine how the mechanism operates in humans and what implications it may have for clinical or therapeutic use. The results provide a detailed explanation of a previously unclear process, advancing scientific understanding of how physical activity influences hunger regulation at the molecular and cellular levels, with potential relevance for obesity, metabolic disorders, and appetite-related conditions. – By Content Syndication Services.