A newly identified cell type fills a critical gap in the brain’s appetite control network.
When you’re contemplating whether to snack on another potato chip, a fierce conflict is occurring in your brain. One set of neurons pushes you towards hunger, whereas another set encourages you to feel full. The speed at which one influences you over the other ultimately affects your decision to stop eating.
Recently, researchers found a crucial element in this complex system that manages hunger and fullness — a novel type of neuron that acts as an immediate counterbalance to your desire to eat. The research, featured in Nature, enhances the traditional understanding of appetite regulation and may unveil new opportunities for addressing obesity and metabolic issues.
“This newly discovered neuron alters our understanding of how feeding is controlled,” explains Han Tan, a research associate at Rockefeller’s Laboratory of Molecular Genetics, led by Jeffrey Friedman.
Managing hunger
Traditionally, it was believed that the brain’s feeding mechanism consisted of a straightforward feedback loop between two types of neurons in the hypothalamus: the AGRP neurons that stimulate hunger and the POMC neurons that signal fullness. Earlier theories proposed that these two groups were primarily influenced by leptin, a hormone involved in weight regulation, but more recent research indicated that this view was too simplistic. The activation of AGRP neurons leads to a swift increase in appetite, while stimulating POMC neurons can take several hours to curb it. This made researchers question whether they had overlooked another factor. “We theorized that POMC might not be able to sufficiently counteract hunger quickly enough,” Tan comments. “Our hypothesis was that there might be an undiscovered neuron responsible for promoting quick feelings of satiety, similar to the speed of AGRP.”
Utilizing single-cell RNA sequencing techniques on neurons in the arcuate nucleus of the brain, the researchers uncovered a previously unknown neuron type that expresses a gene called BNC2 and receptors for leptin, which is known to significantly impact body weight management. This newly identified BNC2 neuron swiftly reacts to food stimuli, serving to quickly reduce hunger.
The research shows that when BNC2 neurons are stimulated by leptin or other signals, they not only decrease appetite but also lessen the unpleasant sensations that come with hunger. Additionally, these neurons manage to suppress hunger by inhibiting AGRP neurons quickly, providing an essential complementary signal.
“This study introduces a valuable new element to the appetite regulation network and enhances our grasp of how leptin diminishes the urge to eat,” Friedman remarks. “It also clarifies how different neurons control feeding across varying timeframes.”
Changing our understanding of hunger
The identification of BNC2 neurons holds significant potential for addressing obesity and metabolic disorders. “We are currently investigating whether we can target these neurons to develop new treatments for obesity or diabetes,” Tan notes, referencing genetic research that connects BNC2 to a higher body mass index and diabetes risks among individuals. The team is also examining the effects of stimulating or inhibiting these neurons on glucose and insulin levels, highlighting the possible therapeutic benefits of adjusting their activity.
This finding could also reshape our understanding of the brain’s regulation of instinctive actions. If BNC2 neurons can coordinate hunger control, it raises questions about the existence of similar neural pathways for other instinctual behaviors, such as grooming or sleeping. Discovering analogous circuits could enhance our comprehension of how the brain orchestrates multifaceted actions across various instinctual behaviors, leading to additional breakthroughs in behavioral neuroscience.
“We now perceive BNC2 and AGRP as the balancing forces in feeding,” Tan concludes.
