A previously unknown population of neurons in the hypothalamus may pave the way for new obesity treatments.
Obesity impacts a staggering 40% of adults and 20% of children in the United States. While emerging therapies are making strides in addressing this widespread issue, significant gaps remain in our understanding of the brain-body mechanisms that regulate appetite.
In a breakthrough discovery, researchers have identified a previously unknown group of neurons in the hypothalamus that play a key role in controlling food intake. These neurons may offer a promising target for future obesity treatments.
Published in the December 5 issue of Nature, the study was conducted by a collaborative team from Rockefeller University’s Laboratory of Molecular Genetics, the Institute for Genome Science (IGS) at the University of Maryland School of Medicine, as well as researchers from New York and Stanford Universities. The team identified a new population of neurons that respond to the hormone leptin. Leptin, a crucial player in hunger regulation, is released by the body’s fat stores and signals the brain to suppress appetite.
Linking Genes, Neurons, and Appetite
“We’ve long known that the hypothalamus—located deep in the brain—plays a role in hunger, hormone levels, stress responses, and body temperature,” said Brian Herb, PhD, a scientist at IGS and a Research Associate of Pharmacology, Physiology, and Drug Development at UMSOM. His research published in 2023 in Science Advances was the first time that scientists used single-cell technology to map the cells in the developing hypothalamus in humans, from precursor stem cells to mature neurons.
“Since our earlier research showed that unique regulatory programs in genes give rise to specialized neuronal populations—it makes sense that this new research discovered a previously unknown set of neurons that regulate energy and food intake,” Dr. Herb added
Through several experiments with mice, the researchers found that this previously unknown neuronal population that express both receptors for leptin and the BNC2 gene not only helps suppress hunger, but also responds to food-related sensory cues, such as food palatability and nutritional status. For example, the researchers used CRISPR-Cas 9 to knock out the leptin receptor (LEPR) in these BNC2 neurons. Those mice ate more and gained more weight than control mice. In addition, researchers added fluorescence to the BNC2 neurons and noticed when they fed mice after fasting, the BCN2 neurons activated, whereas previously known neuronal populations in the hypothalamus did not react.
“These findings add a critical new component to our understanding of how neurons impact appetite and obesity,” Dr. Herb said. “This could be a future target for obesity treatment, such as by activating these neurons to reduce weight or suppress hunger.”
Reference: “Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake” by Han L. Tan, Luping Yin, Yuqi Tan, Jessica Ivanov, Kaja Plucinska, Anoj Ilanges, Brian R. Herb, Putianqi Wang, Christin Kosse, Paul Cohen, Dayu Lin and Jeffrey M. Friedman, 30 October 2024, Nature.
DOI: 10.1038/s41586-024-08108-2
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