Researchers at the Korea Advanced Institute of Science and Technology (KAIST) have demonstrated that the brain is capable of selectively recognizing specific nutrients, particularly glucose, beyond merely detecting caloric intake. As research progresses, it is expected to help regulate appetite or treat metabolic diseases.
The research team, led by Professor Seong-Bae Seo of KAIST’s Department of Biological Sciences, announced on the 9th that they have identified the existence of a gut-brain circuit that induces glucose-deficient animals in a state of hunger to selectively recognize and prefer glucose in the intestine. The study also involved Professor Yeong-Gyun Park from KAIST’s Department of Bio and Brain Engineering, Professor Seung-Hee Lee from the Department of Biological Sciences, and researchers from Albert Einstein College of Medicine in New York.
Living organisms, including humans, derive energy from various nutrients such as sugars, proteins, and fats. Previous studies have revealed that total caloric information in the gut regulates appetite by inhibiting hunger neurons in the hypothalamus. However, the existence of a gut-brain circuit that responds specifically to glucose and the specific brain cells that respond to it have not been identified.
The research team has uncovered a gut-brain circuit that detects glucose, which is essential for brain function, and regulates intake behavior for necessary nutrients. This circuit showed that the brain’s ‘stress response cells (CRF neurons)’ react not only to hunger or external stimuli but also to specific caloric nutrients that directly enter the small intestine, particularly responding selectively to glucose.
The researchers modified genes to enable neurons to activate upon receiving light signals. This method is known as 'optogenetics.' Using this approach, they directly observed the brain's responses to various nutrients, including glucose (D-glucose, L-glucose), amino acids, and fats. As a result, it was confirmed that the CRF neurons in the hypothalamus respond selectively only to D-glucose.
The research team confirmed the circuit through which glucose detection signals from the small intestine are transmitted to the CRF neurons in specific regions of the brain via the spinal cord. In optogenetic inhibition experiments, when the CRF neurons were suppressed in fasting mice, the animals no longer preferred glucose.
Professor Seong-Bae Seo stated, 'This research identifies a glucose-specific gut-brain signaling pathway, which could present new therapeutic targets for metabolic diseases such as obesity and diabetes,' adding, 'In the future, it is expected to expand into research that reveals the presence of similar circuits that detect other essential nutrients such as amino acids and fats, as well as their interaction mechanisms.'
References
Neuron (2025), DOI: https://doi.org/10.1016/j.neuron.2025.05.024