Scientists have long believed that the answer lies almost entirely in neurons, the brain’s main signaling cells. But new research challenges that idea and points to a more complex system involving other types of brain cells.
Research published in Proceedings of the National Academy of Sciences April 6, 2026 Research shows that astrocytes, long considered supporting cells, may play a much more active role in regulating appetite than previously realized.
Researchers from Universidad Concepción in Chile, in collaboration with colleagues from the University of Maryland, have discovered a previously unknown signaling pathway in the hypothalamus, the brain region that controls hunger and satiety. The discovery could ultimately help scientists develop new treatments for conditions such as obesity and eating disorders.
“When people think of how the brain works, they tend to immediately think of neurons,” says Ricardo Arraneda, a professor in UMD’s biology department and corresponding author of the study. “But we now know that astrocytes, which we thought of as just secondary support cells, are also involved in how our brains regulate how much we eat. This study changes the way we think about these communication circuits.”
How the brain detects glucose after eating
This process begins in specialized brain cells known as tunny sites. These cells line fluid-filled cavities deep in the brain and monitor glucose (the sugar that fuels the body) moving through the cerebrospinal fluid.
Blood sugar levels rise after eating. Taneysite processes this sugar and reacts by releasing a metabolic byproduct, lactic acid, into nearby brain tissue. This lactic acid then interacts with neighboring astrocytes and initiates the next stage of communication.
“Researchers thought that the lactic acid produced by tanycytes ‘spoke’ directly to neurons involved in appetite control,” Araneda explained. “But it turns out there’s an unexpected mediator in that conversation: astrocytes.”
Astrocytes function as important messengers in appetite control
Astrocytes are one of the most common cell types in the brain and have traditionally been considered supporting cells for neurons. However, this study shows that they can play a more direct signaling role.
Researchers discovered that astrocytes possess a receptor called HCAR1 that detects lactate. When lactic acid binds to this receptor, astrocytes are activated and release the chemical messenger glutamate. This signal is then transmitted to neurons that suppress appetite, creating a feeling of fullness.
“What surprised us was the complexity,” Araneda said. “Simply put, we found that tunny sites ‘talk’ to astrocytes, which in turn ‘talk’ to neurons. ”
A chain reaction that spreads throughout the brain
In one experiment, scientists introduced glucose into a single tanycyte while observing nearby astrocytes. Even this local change triggers the activity of multiple surrounding astrocytes, showing how signals spread through brain networks.
“We also noticed a kind of double effect,” Arraneda noted. “The hypothalamus contains two opposing populations of hunger-promoting and hunger-inhibiting neurons. We found that lactate may act on both simultaneously, activating satiated neurons through astrocytes and calming hungry neurons through a more direct pathway.”
What this finding means for obesity and eating disorders
Although the study was conducted in an animal model, both tanyocytes and astrocytes are present in all mammals, including humans. This suggests that the same mechanism may be at work in humans.
The research team’s next step is to test whether changes in the HCAR1 receptor on astrocytes affect feeding behavior. This research is essential before potential treatments can be developed.
Currently, there are no drugs that directly target this pathway. But Araneda believes this could be a promising new direction in treating appetite-related diseases.
“We now have another mechanism that may be able to target astrocytes, specifically this HCAR1 receptor,” he added. “This could be a new target that could complement existing treatments like Ozempic, for example, and improve the lives of many people suffering from obesity and other appetite-related conditions.”
10 years of scientific cooperation
These findings are the result of nearly a decade of collaboration between UMD’s Araneda lab and the lab of María de los Ángeles García Robles at the University of Concepción, the project’s principal investigator. The study’s lead author, Sergio López, is a doctoral student who was co-supervised by both researchers and conducted the key experiments during an eight-month research visit to UMD.
The paper “Tannycyte-derived lactate activates HCAR1 in astrocytes and modulates glutamatergic signaling and excitability of POMC neurons.” Proceedings of the National Academy of Sciences April 6, 2026.
This research was funded by Chile’s National Science and Technology Development Fund, the Millennium Neuroscience Institute in Valparaíso, and the U.S. National Institutes of Health (award number R01AG088147A). This article does not necessarily reflect the views of these organizations.
