Scientists have discovered a new type of neuron, BNC2, that acts as a direct counterbalance to hunger neurons and provides a fast-acting satiety mechanism. This discovery expands our understanding of appetite regulation and could pave the way for new treatments for obesity and metabolic disorders.

Your brain is fighting a fierce battle when you decide whether or not to eat more potato chips. One group of neurons triggers hunger, while the other signals satiety. How quickly one side gains the upper hand determines whether you’ll be left with a bag of chips.

Now scientists have identified a missing link in this neural circuit that controls hunger and satiety, a previously unknown type of neuron that acts as a direct counterbalance to the desire to eat. The results were published on: Nature It expands the classical model of hunger and satiety regulation and may offer new therapeutic targets in combating obesity and metabolic disorders.

“This new type of neuron changes the conceptual basis of feeding regulation,” says Han Tan, a research assistant at the Rockefeller Laboratory of Molecular Genetics led by Jeffrey Friedman.

Traditionally, the brain’s so-called feeding circuit was thought to involve a simple feedback loop between two types of brain cells in the hypothalamus: Neurons expressing a gene called AGRP induce hunger, while neurons expressing a gene called POMC promote satiety. These two populations were previously thought to be the two main targets of leptin, but recent studies have shown this model to be incomplete.

While activation of AGRP neurons rapidly triggers appetite, activation of POMC neurons takes hours to suppress appetite. The researchers wondered if they had missed something. “We suspected that the POMC could not stabilize hunger neurons quickly enough to inhibit feeding,” says Tan. “So we wondered whether there was a missing neuron that might contribute to rapid saturation on the same time scale as AGRP.”

By sequencing single-cell RNA of neurons in the arcuate nucleus of the brain, the team discovered a new type of neuron that expresses a gene called BNC2 along with receptors for the hormone leptin, which has previously been shown to play an important role in the body. weight regulation. . This newly discovered BNC2 neuron responds rapidly to food cues and quickly suppresses hunger.

Our results suggest that BNC2 neurons activated by leptin and possibly other signals not only suppress appetite but also reduce negative emotions associated with hunger. Specifically, these neurons act by inhibiting AGRP neurons, and by doing so rapidly they may serve as an additional signal.

“This study adds an important new component to the neural circuits that regulate appetite and expands our understanding of how leptin reduces appetite,” says Friedman. “It also unravels the mystery of how feeding is regulated by different neurons on different time scales.”

Redefining hunger

The discovery of BNC2 neurons has broad implications in combating obesity and metabolic disorders. “We are actively investigating whether targeting these neurons could provide new treatments for obesity or diabetes,” says Tan, noting genetic studies linking BNC2 to high body mass index and risk of diabetes in patients. The team is also investigating how stimulating or inhibiting these neurons affects glucose and insulin levels, further highlighting the therapeutic potential of modulating their activity.

This discovery could also have broad implications for how we understand the brain’s control over instinctive behavior. If BNC2 neurons can coordinate the regulation of hunger, might other similar behavioral patterns exist, such as self-care or sleep? Identifying such circuits could deepen our understanding of how the brain choreographs complex actions in various instinctive behaviors and pave the way for further discoveries in behavioral neuroscience.

“We now think that BNC2 and AGRP are a kind of nutritional yin and yang,” says Tan.