Special neurons controlling fullness while eating hold potential for future obesity treatments

Columbia scientists have discovered that specialized brain neurons in mice tell them to stop eating, which they suggest could lead to new obesity treatments.

“These neurons are unlike any other neuron involved in regulating satiation,” says co-lead researcher Alexander Nectow, a physician-scientist at US Columbia University Vagelos College of Physicians and Surgeons.

“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.”

The researchers also investigated the effects of hormones and other eating circuits on the neurons, discovering that a GLP-1 agonist activated them and a hormone that increases appetite silenced them.

The study in journal Cell looked at neurons located in the brainstem, “the oldest part of the vertebrate brain.”

Discovery of new cells

Nectow questions how the brain knows when the body has eaten enough and then acts to stop eating. “It happens every time we sit down to eat a meal: At a certain point while we’re eating, we start to feel full, and then we get fuller, and then we get to a point where we think, okay, that’s enough.”

In light, the neurons were activated and the mice ate smaller meals.Co-lead author Srikanta Chowdhury, an associate research scientist in the Nectow lab, and Nectow used a new single-cell method known as spatially resolved molecular profiling. Smaller meals were possible for the mice because the neurons were designed to be activated and deactivated by light.

They explain that previous studies tracked decision-making cells to the brainstem but it was difficult, until now, to tell the cells apart. 

“This technique — spatially resolved molecular profiling — allows you to see cells where they are in the brainstem and what their molecular composition looks like,” Nectow explains.

The researchers found unrecognized cells that were similar to other known neurons regulating appetite. “We said, ‘Oh, this is interesting. What do these neurons do?’”

Light-controlled eating 

Using light, the researchers engineered the neurons to turn on and off to see how it influenced eating. 

In light, the neurons were activated and the mice ate smaller meals. Higher intensity of activation would speed up how fast the mice stopped eating.

“Interestingly, these neurons don’t just signal an immediate stop; they help the mice to slow down their eating gradually,” Chowdhury says.

Examining other eating circuits and hormones that impact neurons, the researchers discovered that a hormone that boosts appetite and a GLP-1 agonist both silenced the neurons.

“Essentially, these neurons can smell food, see food, feel food in the mouth and in the gut, and interpret all the gut hormones that are released in response to eating,” Nectow adds. “And ultimately, they leverage all of this information to decide when enough is enough.”

“We think it’s a major new entry point to understanding what it means to be full, how that comes about, and how that is leveraged to end a meal. And we hope that it could be used for obesity therapies down the road.”

He explains that although the specialized neurons were seen in mice, all vertebrates share the same location — the brainstem — suggesting it is highly likely that humans have the same neurons.