New Insights into Brain's Role in Appetite Control Unveil Potential for Obesity Treatments

The connection between fullness and appetite regulation has always intrigued scientists. Traditional understanding emphasized the role of neurons as the primary players in this complex process. However, a recent study offers a fresh perspective, highlighting the active involvement of astrocytes—once deemed mere support cells.

The research, published in the Proceedings of the National Academy of Sciences, established a new pathway in the hypothalamus, the brain's control center for hunger and satiety. Conducted by researchers from the University of Concepción and the University of Maryland, this work could transform future therapies targeting obesity and eating disorders.

"Most people think of neurons when considering how the brain manages appetite," remarked Ricardo Araneda, a professor at UMD and co-author of the study. "Our findings suggest that astrocytes, which we had sidelined as simple support structures, are integral to the brain's signaling networks that regulate food intake."

Decoding the Mechanism: The Role of Tanycytes and Astrocytes

The investigation identified tanycytes, specialized cells lining a cavity in the brain's interior, which monitor glucose levels in the cerebrospinal fluid. After consuming food, glucose concentrations rise, prompting tanycytes to convert this sugar into lactate, which is then released into the surrounding brain area. This lactate acts as a critical communication tool between different cell types.

"Previously, we assumed that lactate merely interacted with neurons responsible for appetite regulation," Araneda explained. "Our results indicate that astrocytes mediate this interaction, acting as an unexpected intermediary."

Astrocytes: More than Just Support Cells

This study showcases astrocytes as active participants in appetite signaling. The researchers found that these cells possess the HCAR1 receptor that detects lactate. When lactate binds to this receptor, astrocytes become activated and release glutamate, a chemical that signals neurons to suppress appetite, thereby inducing the sensation of fullness.

"The layered complexity of this system surprised us," noted Araneda. "Essentially, we discovered that tanycytes relay signals to astrocytes, which then convey messages to appetite-regulating neurons."

Moreover, the researchers demonstrated that even minor fluctuations in glucose levels could trigger responses in clusters of astrocytes, indicating a highly interconnected network of communication within the brain.

The Implications for Appetite Regulation and Health

Interestingly, the research also revealed that lactate may affect both appetite-promoting and appetite-suppressing neurons. "The hypothalamus harbors two opposing neuron populations: one that encourages hunger and another that quells it. Lactate might stimulate fullness signals while simultaneously damping hunger responses," Araneda added.

While the findings were derived from animal models, both tanycytes and astrocytes are present in humans, suggesting that the mechanisms observed could translate to human biology. The next phase for this research team is to explore whether modifications to the HCAR1 receptor in astrocytes could alter eating behaviors, laying the groundwork for novel therapeutic options.

At present, no medications specifically target this newly identified pathway. However, Araneda sees promise in the potential for new treatments that focus on astrocytes and the HCAR1 receptor, which could complement existing therapies like Ozempic, offering hope to those grappling with obesity and related conditions.

This research has stemmed from a decade-long collaboration between Araneda's lab at UMD and María de los Ángeles García-Robles' team at the University of Concepción. Lead author Sergio López, a doctoral candidate co-mentored by both professors, conducted critical experiments during his research stay at UMD.

The paper titled "Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability" was officially published on April 6, 2026, in the Proceedings of the National Academy of Sciences.

This work has received funding support from 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). The views expressed in this article do not necessarily reflect the organizations' positions.

Materials provided by University of Maryland. Note: Content may be edited for style and length.