The US Food and Drug Administration-approved drug liraglutide has been shown to help obese patients lose weight by suppressing their appetite. However, where and how the drug acts in the brain was not fully understood, until now.

A new preclinical study from the Perelman School of Medicine, published in Science Translational Medicine, shows how liraglutide crosses the brain’s blood barrier to engage with a region of the brainstem known as the nucleus tractus solitarius (NTS), which is responsible for balancing food intake and energy expenditure. Filling this gap meets a need that has become a priority for researchers looking for new treatments to help fight the increasing rates of obesity.

Liraglutide interacts with targets called glucagon-like peptide-1 receptors (GLP-1R) in various parts of the brain to suppress hunger. This is the first study to show how a distinct group of neurons that express GLP-1Rs within the NTS of the brainstem play a key role in mediating these effects.

“This discovery opens up the door for future obesity drug treatments that could be used in conjunction with this FDA-approved therapy to treat obesity,” says senior author Matthew R. Hayes, an associate professor of psychiatry at Penn. “The more we understand how drugs act, the more we can understand what other brain systems can be manipulated in combination with them to help patients lose more weight.”