Researchers have identified a new group of neurons that respond to the hormone leptin, which plays a crucial role in managing obesity. Leptin is produced by the body’s fat stores and is sent to the brain to help reduce appetite.
In the United States, obesity impacts an alarming 40 percent of adults and 20 percent of children. Although various new treatments are emerging to address the obesity crisis, there remains much to learn about the intricate connection between the brain and the body’s regulation of hunger. Recently, scientists uncovered a previously undiscovered set of neurons in the hypothalamus that influence food intake and may serve as a promising target for obesity-related medications.
A study featured in the Dec. 5 issue of Nature highlights the collaborative efforts of researchers from the Laboratory of Molecular Genetics at Rockefeller University in New York, the Institute for Genome Science (IGS) at the University of Maryland School of Medicine (UMSOM) in Baltimore, along with teams from New York University and Stanford University. They discovered this new group of neurons that react to leptin, thereby playing a significant role in obesity management.
“We’ve always known that the hypothalamus, situated deep within the brain, is crucial for hunger regulation, hormone balance, stress responses, and body temperature control,” explained Brian Herb, PhD, a scientist at IGS and a Research Associate of Pharmacology, Physiology, and Drug Development at UMSOM. His prior work, published in 2023 in Science Advances, marked the first instance of scientists employing single-cell technology to map the development of hypothalamic cells in humans, from stem cells to fully formed neurons.
“Our previous findings indicated that distinct regulatory gene programs lead to specialized neuronal populations, which supports the discovery of this new group of neurons that manage energy and food consumption,” Dr. Herb noted.
Through a series of experiments on mice, the researchers observed that this newly identified neuronal group, which expresses both leptin receptors and the BNC2 gene, not only helps curb appetite but also reacts to sensory inputs related to food, such as taste and nutritional content. For instance, the team utilized CRISPR-Cas9 technology to disable the leptin receptor (LEPR) within these BNC2 neurons, which resulted in the mice eating more and gaining additional weight compared to a control group. Furthermore, by adding fluorescence to the BNC2 neurons and feeding the mice after periods of fasting, the researchers found that these neurons activated while previously known groups in the hypothalamus did not show any response.
“BNC2 neurons in the hypothalamus, which are triggered by leptin, present the opportunity for a completely new type of obesity medication,” stated Mark T. Gladwin, MD, who serves as the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, as well as Vice President for Medical Affairs at the University of Maryland, Baltimore. “These medications would differ from Ozempic and other GLP-1 agonists that promote insulin secretion. Drugs that target leptin could provide relief for individuals unable to tolerate GLP-1 agonists due to gastrointestinal issues like nausea and stomach discomfort.”
