Brain Circuit That Regulates Appetite-Related Memories Discovered: "Potential New Obesity Drug Target Beyond GLP-1"

U.S. team identifies the "memory–appetite linkage circuit"
GLP-1 found to regulate not only satiety but also "memory-based appetite"

Researchers have identified a brain circuit that can rekindle memories of pleasurable eating and thereby increase or suppress appetite. They have pinpointed nerve cells that regulate appetite by linking past experiences with place-related memories.

U.S. researchers identified a brain circuit that, by reactivating memories of eating tasty food, can either stimulate or suppress appetite. AI-generated image

The analysis suggests that binge eating and obesity may not be simply a matter of willpower, but could be related to abnormalities in memory-based brain circuits. The newly discovered brain circuit is being discussed as a potential new target for next-generation obesity treatments.

A joint research team from Massachusetts General Hospital (MGH) and the Broad Institute has discovered a circuit of “prodynorphin-secreting neurons” that converts memory information into appetite-regulating signals. The findings were published in the international journal Neuron on February 12 (local time).

The researchers focused on the lateral septum, a region that connects the hippocampus, which is responsible for memory in the brain, with the hypothalamus, which governs appetite. They confirmed that “prodynorphin (Pdyn) neurons” located in this area play a key role in reflecting memories of past feeding experiences and places onto current appetite.

When these neurons were inhibited or removed in laboratory mice, their memory of locations where they had previously eaten weakened. In unfamiliar environments, binge-eating behavior increased markedly. Conversely, when the neurons were stimulated, food intake decreased and avoidance behavior appeared. The researchers concluded that the neurotransmitters released by these neurons act as signals that suppress appetite by lowering the rewarding feeling of food.

The team also found that prodynorphin neurons express glucagon-like peptide-1 (GLP-1) receptors, which are attracting attention as targets for anti-obesity drugs. This suggests that GLP-1 agonists may do more than simply enhance satiety; they may also affect brain circuits that regulate appetite based on memories of past eating experiences and contextual situations.

The researchers explained that binge eating disorder or obesity can occur when this “memory–appetite circuit” does not function properly. When the circuit works normally, the brain sends appetite-suppressing signals to regulate food intake when memories of eating in a particular place are recalled. However, if the circuit is impaired, these signals may be cut off, making it impossible to control appetite even when one is already full.

The research team stated, “This study has revealed the neural pathway in the brain through which past memories influence current meal choices,” adding, “It could offer a new therapeutic option for patients with eating disorders who struggle to control their appetite in specific situations.”

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