Feeling full after a meal is healthy and normal, but what causes that feeling is complicated and previously not well understood. University of Arizona-led research published in the journal Molecular Metabolism has identified a brain region and neural circuitry that mediates satiety, which could help scientists better target drugs to treat eating disorders or manage weight.
Previous research has mapped satiation to the brain’s central amygdala, which also controls fear, pain and other strong emotions. But the complexity of the neurons in this part of the brain has made it difficult for scientists to identify where the signal goes next.
“When we can more precisely target the part of the brain responsible for feelings of satiation, then we can create treatments with fewer side effects,” said lead study author Haijiang Cai, an associate professor in the Department of Neuroscience.
Cai and his team found that after the amygdala, the signal heads to neurons located in a brain region called the parasubthalamic nucleus, or PSTh, responsible for the feeling of satiation.
The PSTh region of the brain was first discovered by Chinese scientists in the 1990s and was introduced in English-language scientific literature in 2004, but its function was unknown.
Here’s how they did it: First, they knew that the hormone cholecystokinin, or CCK, is secreted by the gut to tell the brain “I’m full” after a meal. They also knew that specific neurons in the amygdala, called PKC-delta neurons, mediate the satiation effect of CCK by turning off other central amygdala inhibitory neurons. The researchers reasoned that the neurons downstream of the central amygdala should be turned on by PCK-delta neurons while also being turned on by CCK, Cai said.
“We found the neurons in this region are required for the CCK satiation to suppress feeding. We know this because if we silence these neurons and the subject keeps eating, then CCK does not have any effect. But if we also directly activated these neurons and the subject stops eating, then it suggests these neurons play a very important role in regulated satiation,” Cai said.
Feeling satiated is so important that Cai doubts it is mediated by a single brain region; it is more likely multiple brain regions working together. He stressed that the PSTh is likely just one piece in a larger puzzle that controls the feeling of satiation.