A recent study has identified the specific neurons in the brain responsible for the common side effect of nausea caused by next-generation anti-obesity drugs like Wegovy. These drugs, which mimic a hormone called glucagon-like peptide 1 (GLP-1), are effective in weight loss but can also lead to intolerable nausea and food aversion.
The research found that the brain circuit that induces nausea and food aversion is separate from the circuit that produces feelings of fullness and satiety. By selectively targeting the satiety circuits without affecting the aversion circuits, scientists hope to develop weight-loss drugs with fewer side effects in the future.
The study involved killing neurons with GLP-1 receptors in specific regions of the brains of mice and then administering GLP-1-mimicking drugs like semaglutide or exenatide. Surprisingly, it was discovered that the hindbrain, rather than the hypothalamus as previously believed, is the primary site of action for these drugs.
Further investigation revealed that turning on the animals’ area postrema (AP) neurons in the hindbrain led to nausea and food aversion, while activating the nucleus of the solitary tract (NTS) neurons resulted in reduced food intake without nausea. This suggests that nausea is not a necessary component for the suppression of food intake by GLP-1 drugs.
The potential to develop weight-loss medications that specifically target the satiety circuits while avoiding the aversion circuits could lead to more effective and tolerable treatments for obesity. Researchers are now focused on finding ways to selectively activate the desired neurons to minimize side effects and improve patient outcomes.
Overall, this groundbreaking study sheds light on the complex brain pathways involved in the side effects of anti-obesity drugs and paves the way for the development of safer and more efficient medications in the future. By understanding the distinct neuronal pathways responsible for different effects, scientists are one step closer to revolutionizing obesity treatment and improving the lives of individuals struggling with weight management issues.
