"Hunger neurons" have an unexpected role in the action of Ozempic, study shows

A recent study has revealed that neurons associated with hunger play an unexpected role in the effectiveness of Ozempic, a popular weight-loss medication based on semaglutide. The findings suggest that these drugs might function in a more complex manner than previously assumed. While their effects have largely been attributed to appetite suppression, new research on mice indicates that long-term weight loss does not depend solely on reducing hunger, according to Science Alert. The unexpected role of "hunger neurons" Published in the journal PNAS, the study highlights that brain cells known as "hunger neurons" must remain functional for semaglutide to achieve its full effect on weight reduction. This finding initially seems contradictory, raising questions about why a weight-loss drug would rely on neurons that promote hunger. More than just the feeling of hunger In the study, Mateus d'Ávila from Yale University and his colleagues examined brain cells that regulate the body's energy balance. These neurons, scientifically known as AgRP neurons, become active when the body lacks energy. "AgRP neurons are often described simply as 'hunger neurons,' but this is an oversimplification," explained d'Ávila. "Previous work from our lab, as well as other teams, has shown that these neurons coordinate a broader response to energy deficits. This includes how the body activates and uses stored energy, such as fat reserves." Key experiment on mice Scientists disrupted the function of AgRP neurons in female mice and then administered semaglutide. This drug mimics a natural hormone released after meals that signals satiety to the brain. Its effects include reduced appetite, slowed gastric emptying, and assistance in regulating blood sugar levels. During treatment, female mice with blocked "hunger neurons" still ate less. However, their metabolic response was weakened, and they regained lost weight within 15 days. In contrast, mice with functional neurons maintained lower body mass. Researchers were most surprised to find that mice regaining weight continued to consume less food, sometimes even less than the control group. This indicated that the full effect of semaglutide on body weight in female mice could not be explained solely by reduced food intake. When AgRP neurons were non-functional, the body’s ability to use energy from fat stores decreased. Confirmation of mechanism and limitations The team confirmed their findings through additional experiments. It was found that disrupting hunger neurons or blocking pathways for using fat stores weakens the drug’s effect on body weight. Scientists also noted that long-term semaglutide therapy alters cell activity, energy expenditure, and connections between AgRP cells and other neurons. However, the study has important limitations. Experiments were conducted on mice, not humans, and the most notable effect was observed in females. Males under similar conditions did not show the same results. Diet and methods used to block neurons also influenced outcomes. "This is a preclinical study on the mechanism of action, and our results should not yet be used as guidelines for taking semaglutide or other GLP-1 drugs in humans," emphasized d'Ávila. Broader scientific context Researchers did not directly compare semaglutide with older appetite-suppressing drugs, so it is premature to conclude that the discovered mechanism explains the longer-lasting effects. Previous studies help place these unexpected results into context. A 2025 study found that fast-acting GLP-1 drugs quickly block AgRP neurons, and stronger blockade is linked to greater reductions in food intake. When scientists artificially reactivated these neurons, animals partially regained their appetite. Another study on mice identified a separate group of neurons in the hypothalamus crucial for semaglutide’s effect on appetite and weight, but not for side effects like nausea. Implications for future therapies The new study does not dispute previous findings regarding the short-term impact on appetite. However, it opens avenues for understanding how these drugs affect metabolism over time. Future research may explore ways to enhance the metabolic benefits of semaglutide while minimizing potential side effects. Wegovy, another weight-loss drug containing semaglutide, functions similarly to Ozempic. It is increasingly popular among individuals with overweight or obesity. Wegovy works by suppressing appetite and is often used in combination with exercise or dietary changes. It can also help prevent heart attacks or strokes in overweight individuals and treat fatty liver disease. Wegovy is prescribed for people with a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher with certain health issues such as diabetes, high blood pressure, elevated cholesterol levels, sleep apnea, and others. It is also available for adolescents whose BMI exceeds that of 95 percent of children of the same age or who weigh more than 60 kilograms. Wegovy is administered via weekly injections, typically under the skin on the abdomen, thighs, or upper arms. The dosage increases over time, starting at 0.25 milligrams per injection and reaching 2.4 milligrams after five months of use. However, weight regain is common once the medication is discontinued, emphasizing the importance of adopting healthy lifestyle habits alongside the drug. The European Commission has approved a daily tablet version of Wegovy, although it is generally less effective than the injectable form. Wegovy is not covered by public health insurance and must be purchased at full price, ranging from 143 to 244 euros depending on the dose. Common side effects include headache, nausea, vomiting, diarrhea, constipation, or abdominal pain, which usually subside as the body adjusts. Long-term use may lead to more serious complications such as pancreatitis, kidney problems, gallbladder disease, intestinal inflammation, or increased risk of thyroid cancer. Individuals with thyroid cancer or pregnant women should avoid the drug. Wegovy is used primarily for weight management and treating specific medical conditions. It requires a prescription from a healthcare provider and is not available through public health insurance. Patients must pay the full cost of the medication.