Feeling full, or satiated, after a meal is healthy and normal, but what
causes that feeling is complicated and not well understood. New University
of Arizona-led research published in the journal Molecular Metabolism has
identified a brain region and neural circuitry that mediate satiation, which
could help scientists better target drugs to treat eating disorders or
manage weight.
There are currently six Food and Drug Administration-approved medications
for weight management, but they often come with side effects.
"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 and BIO5 Institute member.
Previous research has mapped the circuits for 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 map where the signal goes next.
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.
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.
In mouse models, the researchers determined that the neurons activated by
CCK and PKC-delta neurons were located in the parasubthalamic nucleus.
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.
"We found the neurons in this region are required for the CCK satiation to
suppress feeding," Cai said. "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."
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.
Cai began studying the neurocircuitry of eating because he was interested in
the role emotions play in our eating habits.
"We know that eating and emotions are different behaviors, but they interact
closely with each other," he said. "Some people eat when stressed, while
others eat less. Some people with an eating disorder or obesity have
abnormal eating behavior, but they also have emotional problems. So, we hope
to identify the neural mechanisms that control eating and control emotion
and how they interact with each other. This knowledge can help us develop a
more specific treatments."
Reference:
Sanchez MR, Wang Y, Cho TS, et al. Dissecting a disynaptic central
amygdala-parasubthalamic nucleus neural circuit that mediates
cholecystokinin-induced eating suppression. Mol. Metab. 2022;58:101443.
DOI: 10.1016/j.molmet.2022.101443
Tags:
Biology & Health