Neurons that tell you to stop eating could unlock obesity treatments

Good news! This could be a breakthrough!

"... Using a new technique called spatially resolved molecular profiling, the ...  scientists were able to peer into the brainstem – which connects the brain to the spinal cord and controls vital functions – and discern the different types of cells in there, down to their molecular composition. This was previously not possible. ...

Specifically, as the researchers noted "... a population of neuropeptidergic neurons in the brainstem’s dorsal raphe nucleus (DRN)" ... "These neurons track food from sensory presentation through ingestion, integrate these signals with slower-acting humoral cues, and express cholecystokinin (CCK)," ... "These CCK neurons bidirectionally regulate meal size, driving a sustained meal termination signal with a built-in delay." ...

Those CCK neurons are activated by Exendin-4, a GLP-1 agonist. This suggests that one way GLP-1 agonists like Ozempic reduce appetite is by activating these specific CCK neurons. ..."

"... Though many feeding circuits in the brain are known to play a role in monitoring food intake, known neurons in those circuits do not make the final decision to cease eating a meal.

The newly identified neurons, a new element of these circuits, are located in the brainstem, the oldest part of the vertebrate brain. Their discovery could lead to new treatments for obesity.

“These neurons are unlike any other neuron involved in regulating satiation,”  ...

“Other neurons in the brain are usually restricted to sensing food put into our mouth, or how food fills the gut, or the nutrition obtained from food. The neurons we found are special in that they seem to integrate all these different pieces of information and more.” ..."

From the highlights and abstract:

"Highlights

• In situ molecular phenotyping of DRN at transcriptional and translational levels

• An obligate peptidergic population in the DRN is delineated by CCK expression

• CCK neurons track each bite of food to promote satiation via delayed signaling

• CCK neurons regulate satiation through multiple negative feedback loops

Summary

Hunger is evolutionarily hardwired to ensure that an animal has sufficient energy to survive and reproduce. Just as important as knowing when to start eating is knowing when to stop eating.

Here, using spatially resolved single-cell phenotyping, we characterize a population of neuropeptidergic neurons in the brainstem’s dorsal raphe nucleus (DRN) and describe how they regulate satiation.

These neurons track food from sensory presentation through ingestion, integrate these signals with slower-acting humoral cues, and express cholecystokinin (CCK). These CCK neurons bidirectionally regulate meal size, driving a sustained meal termination signal with a built-in delay. They are also well positioned to sense and respond to ingestion: they express a host of metabolic signaling factors and are integrated into an extended network known to regulate feeding.

Together, this work demonstrates how DRN CCK neurons regulate satiation and identifies a likely conserved cellular mechanism that transforms diverse neurohumoral signals into a key behavioral output."

Neurons that tell you to stop eating could unlock obesity treatments "Researchers at Columbia University Irving Medical Center have identified the specific neurons in mice brains that tell them they've eaten enough. This fascinating discovery could play a big role in the future of weight loss treatments for humans."

These Neurons Send Order to Stop Eating (original news release)

Brainstem neuropeptidergic neurons link a neurohumoral axis to satiation (no public access)

Graphical abstract