Summary: Scientists have uncovered a new neuron type, BNC2, which acts quickly to counter hunger-promoting neurons, potentially leading to more effective appetite regulation. These BNC2 neurons, located in the brain’s arcuate nucleus, respond rapidly to hunger cues by inhibiting AGRP neurons responsible for driving appetite.
This discovery adds a crucial layer to our understanding of the neural circuits controlling hunger and opens the door for novel treatments for obesity and metabolic conditions. The study suggests that BNC2 neurons could counterbalance hunger urges in a matter of minutes, providing a faster response than traditional satiety-promoting neurons.
Researchers hope that by targeting BNC2 neurons, they can develop therapies to better regulate appetite and reduce disease risk. This breakthrough could reshape our understanding of brain-driven behaviors.
Key Facts:
- Rapid response: BNC2 neurons act within minutes to inhibit hunger, faster than previously known satiety neurons.
- Therapeutic potential: BNC2 may provide a novel target for obesity and diabetes treatments.
- Broader implications: Discovering BNC2 neurons hints at similar circuits for other instinctive behaviors.
Source: Rockefeller University
As you’re deciding whether to eat one more potato chip, a pitched battle takes place in your brain. One group of neurons promotes hunger while another induces satiety. How quickly one group gains the upper hand determines how likely you are to put down the bag of chips.
Now, scientists have discovered a missing link in this neural circuit governing hunger and satiety—a previously unidentified type of neuron that serves as an immediate counterbalance to the urge to eat.
The findings, published in Nature, expand the classic model of hunger and satiety regulation, and may provide new therapeutic targets for tackling obesity and metabolic disorders.
“This new type of neuron changes the conceptual framework for how feeding is regulated” says Han Tan, a research associate in Rockefeller’s Laboratory of Molecular Genetics, headed by Jeffrey Friedman.
More or less
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 named AGRP drive hunger and neurons expressing a gene named POMC promote satiety.
Previously these two populations were thought to be the two main targets of leptin but recent studies suggested that this model was incomplete. While activating AGRP neurons rapidly induces appetite, activating POMC neurons takes hours to suppress appetite. Researchers wondered whether they had missed something.
“We suspected POMC couldn’t counterbalance the hunger neurons quickly enough to curb feeding,” Tan says.
“So we wondered if there was a missing neuron that could promote rapid satiety, on a similar timescale to that of AGRP.”
Through single-cell RNA sequencing of neurons in the brain’s arcuate nucleus, the team identified a new type of neuron that expresses a gene called BNC2 together with receptors for the hormone leptin, which has previously been shown to play a significant role in regulating body weight. This newly discovered BNC2 neuron rapidly responds to food cues and acts to rapidly inhibit hunger.
The findings reveal that BNC2 neurons, when activated by leptin and possibly other signals, not only suppress appetite but also alleviate the negative feelings associated with hunger. Remarkably, these neurons act by inhibiting the AGRP neurons and they can do so rapidly, serving as a complementary signal.
“This study has added an important new component to the neural circuit that regulates appetite and broadens our understanding of how leptin reduces appetite,” Friedman says.
“It also solves a mystery about how feeding is regulated on different time scales by different neurons.”
Redefining hunger
The discovery of BNC2 neurons has broad implications for tackling obesity and metabolic disorders.
“We are actively researching whether targeting these neurons could provide a new therapy for obesity or diabetes,” Tan says, pointing to genetic studies that link BNC2 to high body mass index and diabetes risk in patients.
The team is also exploring how stimulating or inhibiting these neurons affects glucose and insulin levels, further underscoring the therapeutic potential of modulating their activity.
This discovery could also have broad implications for how we understand the brain’s control over instinctive behaviors. If BNC2 neurons can coordinate hunger regulation, could there be other similar circuits for behaviors like grooming or sleeping?
Identifying similar circuits could deepen our understanding of how the brain choreographs complex actions across different instinctive behaviors, paving the way for further discoveries in behavioral neuroscience.
“We now believe BNC2 and AGRP to be the sort of yin and yang of feeding,” Tan says.
About this hunger and neuroscience research news
Author: Katherine Fenz
Source: Rockefeller University
Contact: Katherine Fenz – Rockefeller University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake” by Han Tan et al. Nature
Abstract
Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake
Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism.
Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect.
This has raised the possibility that there is a heretofore unidentified leptin-regulated neural population that rapidly suppresses appetite.
Here we report the discovery of a new population of leptin-target neurons expressing basonuclin 2 (Bnc2) in the arcuate nucleus that acutely suppress appetite by directly inhibiting AGRP neurons.
Opposite to the effect of AGRP activation, BNC2 neuronal activation elicited a place preference indicative of positive valence in hungry but not fed mice. The activity of BNC2 neurons is modulated by leptin, sensory food cues and nutritional status.
Finally, deleting leptin receptors in BNC2 neurons caused marked hyperphagia and obesity, similar to that observed in a leptin receptor knockout in AGRP neurons.
These data indicate that BNC2-expressing neurons are a key component of the neural circuit that maintains energy balance, thus filling an important gap in our understanding of the regulation of food intake and leptin action.
