New type of brain cell may tell us when to stop eating

Neurons in the brains of mice tell them to stop eating when they’ve had enough food – and since people probably have the same cells, we might one day manipulate them to help treat obesity.

“The major question that we were seeking to answer was how the brain senses and responds to different signals,” says Alexander Nectow at Columbia University in New York.

To learn more, he and his colleagues used a type of molecular profiling to distinguish between different cell types in the brains of mice. In the dorsal raphe nucleus – a part of the brainstem linked to functions including eating, mood and sleep – they came across cells that produce a hormone called cholecystokinin, which helps regulate appetite.

To study what these cells are sensing to kick them into action, the researchers measured their activity as the mice went about their day. “Every time the animals went for a bite of food, the activity ramped up and then decayed,” says Nectow. “We are able to show that these neurons sense things like the smell and sight of food, the taste of food, the sensation of food in the gut and the neural hormones that are released in response to food in the gut, and leverage that information to actually terminate a meal.”

Next, the researchers used a technique called optogenetics, which involves engineering the neurons so they could be switched on and off with light. When they used light to activate them, the mice slowed down their eating. The more intense the activation, the faster the animals slowed and then stopped.

Because the neurons sit in the brainstem, an ancestral feature that is similar across vertebrates, Nectow thinks we probably also have them. “Even though we haven’t confirmed it, my guess would be that humans have these neurons, certainly.”

The team also found that the mouse neurons could be activated by a compound called a glucagon-like peptide-1 (GLP-1) agonist, a type of drug used to treat obesity and type 2 diabetes, the most familiar being semaglutide, sold under brand names such as Ozempic and Wegovy.

If these neurons have the same function in people, we could in theory modulate them to control eating habits in those with obesity or even combine this approach with GLP-1 based drugs, to achieve greater weight loss, says Nectow.

“Understanding the circuitry that governs the cessation of eating is particularly important in environments of almost ubiquitous food availability,” says Jeff Davies at Swansea University, UK. “The authors used an elegant method to identify these important cell populations.”

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