Researchers Discover New Neurons that Suppress Food Intake

A Previously Unknown Population of Neurons in the Hypothalamus Could Lead to New Obesity Treatments

Obesity affects a staggering 40 percent of adults and 20 percent of children in the United States. While some new popular therapies are helping to tackle the epidemic of obesity, there is still so much that researchers do not understand about the brain-body connection that regulates appetite. Now, researchers have discovered a previously unknown population of neurons in the hypothalamus that regulate food intake and could be a promising new target for obesity drugs.

In a study published in the Dec. 5 issue of Nature, a team 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, as well as New York and Stanford Universities discovered a new population of neurons that is responsive to the hormone leptin. Leptin responsive neurons are important in obesity since leptin is sent to the brain from the body’s fat stores to suppress hunger.

“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.

“BNC2 neurons in the hypothalamus, which are activated by the hunger hormone leptin, provide the potential for a completely new class of obesity drugs," said  Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore. "These drugs would be distinct from Ozempic and other GLP-1 agonists, which stimulate insulin secretion. Leptin-targeting drugs could be beneficial for those who can’t tolerate GLP-agonists due to gastrointestinal side effects like nausea and stomach upset.”

About the Institute for Genome Sciences

The Institute for Genome Sciences' (IGS) has been part of the University of Maryland School of Medicine (UMSOM) since 2007. IGS scientists work in diverse areas, applying genomics and systems biology approaches to better understand health issues in premature infants, women, and transgender people; to improve vaccine development; to study evolutionary biology; and to understand cancer, parasitic, fungal, and infectious diseases, as well as identifying the underpinnings of aging, brain development, addiction, and mental health. IGS also remains at the forefront of high-throughput genomic technologies and bioinformatics analyses through its core facility, Maryland Genomics which provides researchers around the world with cutting-edge, collaborative, and cost-effective sequencing and analysis.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has more than $500 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2023, the UM School of Medicine is ranked #10 among the 92 public medical schools in the U.S., and in the top 16 percent (#32) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit: medschool.umaryland.edu.