For years, scientists believed the answer centered almost entirely on neurons, the brain’s primary signaling cells. But new research is challenging that idea, pointing to a more complex system involving other types of brain cells.
A study published in the Proceedings of the National Academy of Sciences on April 6, 2026, shows that astrocytes, which have long been considered support cells, may play a much more active role in regulating appetite than previously recognized.
Researchers from the University of Concepción in Chile, working with colleagues at the University of Maryland, uncovered a previously unknown signaling pathway in the hypothalamus, the brain region that controls hunger and fullness. The findings could eventually help scientists develop new treatments for conditions such as obesity and eating disorders.
“People tend to immediately think of neurons when they think about how the brain works,” said Ricardo Araneda, a professor in UMD’s Department of Biology and a corresponding author of the study. “But we’re finding that astrocytes, what we used to think of as just secondary support cells, are also participating in how our brains regulate how much we eat. This research changes how we think about these communication circuits.”
How the Brain Detects Glucose After Eating
The process begins with specialized brain cells known as tanycytes. These cells line a fluid-filled cavity deep within the brain and monitor glucose (the sugar that fuels the body) as it moves through cerebrospinal fluid.
After a meal, glucose levels rise. Tanycytes respond by processing this sugar and releasing lactate, a metabolic byproduct, into nearby brain tissue. This lactate then interacts with neighboring astrocytes, setting off the next stage of communication.
“Researchers used to think that lactate produced from tanycytes ‘spoke’ directly to neurons involved in appetite control,” Araneda explained. “But we found that there was an unexpected middleman in that conversation, astrocytes.”
Astrocytes Act as Key Messengers in Appetite Control
Astrocytes are among the most common cell types in the brain and have traditionally been viewed as support cells that assist neurons. However, this study shows they can take on a more direct signaling role.
The researchers found that astrocytes carry a receptor called HCAR1 that detects lactate. When lactate binds to this receptor, astrocytes become activated and release glutamate, a chemical messenger. This signal is then passed to neurons that suppress appetite, leading to the sensation of fullness.
“What surprised us was the complexity of it,” Araneda said. “To put it simply, we found that tanycytes ‘talk’ to astrocytes, and then astrocytes ‘talk’ to neurons.”
A Chain Reaction That Spreads Across the Brain
In one experiment, scientists introduced glucose into a single tanycyte while observing nearby astrocytes. Even this localized change triggered activity in multiple surrounding astrocytes, showing how signals can spread through the brain’s network.
“We also noticed a dual effect of sorts,” Araneda noted. “The hypothalamus contains two opposing populations of neurons: those that promote hunger and those that suppress it. We found that it might be possible that lactate can work on both simultaneously — activating the fullness neurons through astrocytes, while potentially quieting the hunger neurons through a more direct route.”
What This Discovery Could Mean for Obesity and Eating Disorders
Although the research was conducted in animal models, both tanycytes and astrocytes exist in all mammals, including humans. This suggests the same mechanism could be at work in people.
The next step for the research team is to test whether altering the HCAR1 receptor in astrocytes can influence eating behavior. This work is essential before any potential therapies can be developed.
Currently, no drugs directly target this pathway. However, Araneda believes it could become a promising new direction for treating appetite-related conditions.
“We now have a different mechanism where we might be able to target astrocytes or specifically this HCAR1 receptor,” he added. “It would be a novel target that may complement existing therapies like Ozempic, for example, and improve the lives of many who suffer from obesity and other appetite-related conditions.”
A Decade-Long Scientific Collaboration
These findings are the result of nearly ten years of collaborative work between Araneda’s lab at UMD and the laboratory 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 co-mentored by both researchers who carried out key experiments during an eight-month research visit to UMD.
The paper, “Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability,” was published in the Proceedings of the National Academy of Sciences on April 6, 2026.
This research was funded by Chile’s National Fund for Scientific and Technological Development, the Millennium Institute of Neuroscience in Valparaíso and the U.S. National Institutes of Health (Award No. R01AG088147A). This article does not necessarily reflect the views of these organizations.