Obesity impacts 40% of adults and 20% of children in the U.S. While new therapies are helping combat the obesity crisis, there is still limited understanding of the brain-body mechanisms that control appetite. Researchers have recently identified a new group of neurons in the hypothalamus that regulate food intake, presenting a potential new target for obesity treatments.
Researchers from Rockefeller University, the University of Maryland School of Medicine, and New York and Stanford Universities have discovered a new population of neurons that respond to the hormone leptin. Leptin is crucial in regulating obesity, as it is released from the body’s fat stores to signal the brain and suppress hunger.
Brian Herb, PhD, a scientist at IGS and a Research Associate of Pharmacology, Physiology, and Drug Development at UMSOM, said, “We’ve long known that the hypothalamus—located deep in the brain—plays a role in hunger, hormone levels, stress responses, and body temperature.”
In 2023, researchers used single-cell technology for the first time to map the cells in the developing hypothalamus in humans, from precursor stem cells to mature neurons. Their research has shown that unique regulatory programs in genes give rise to specialized neuronal populations.
This new research discovered that a previously unknown population of neurons, which express both leptin receptors and the BNC2 gene, helps suppress hunger and responds to food-related sensory signals, such as food palatability and nutritional status.
Using CRISPR-Cas9, the researchers knocked out the leptin receptor (LEPR) in these BNC2 neurons, leading to increased food intake and weight gain in mice compared to controls. Additionally, by adding fluorescence to the BNC2 neurons, they observed that these neurons activated when mice were fed after fasting, while other known neuronal populations in the hypothalamus did not respond.
Dr. Herb said, “These findings add a critical new component to our understanding of how neurons impact appetite and obesity. This could be a future target for obesity treatment, such as activating these neurons to reduce weight or suppress hunger.”
Journal Reference:
- Tan, H.L., Yin, L., Tan, Y., et al. Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake. Nature 636, 198–205 (2024). DOI: 10.1038/s41586-024-08108-2
