Maya BluittOzempic, Wegovy, Mounjaro, Zepbound – these drugs have recently risen to stardom given their miraculous ability to cause weight loss.
This class of drugs relies on a system revolving around a hormone called glucagon-like peptide-1 (GLP-1). GLP-1 is released into the bloodstream after eating, targeting GLP-1 receptors that exist throughout the body and the brain. One of the effects of GLP-1 receptor activation is increased production and release of insulin from the pancreas, effectively lowering blood sugar. This feature of the GLP-1 system explains why scientists first went after creating GLP-1 drugs in an attempt to treat diabetes.
GLP-1 drugs aren’t only effective at stimulating insulin release. They also slow down movement of food through the stomach after eating (also referred to as gastric emptying), making you feel full for longer. Not only that, but patients who take GLP-1 drugs often report thinking less about food. These additional benefits have led to the use of GLP-1 drugs in treating obesity and promoting weight loss.
While GLP-1 drugs have vast benefits for treating obesity and diabetes, they aren’t without their undesirable consequences. Gastrointestinal symptoms, including nausea, are among the most frequently reported side effects, and lead some people to stop treatment. One might guess that this side effect could also contribute to the effectiveness of the drug, as nausea is often accompanied by a loss of appetite. But a recent study found that there might be a way to tease apart the brain mechanisms that signal feeling full and that drive aversive states like nausea.
In this study, the researchers focused on three brain regions that GLP-1 drugs directly target and are thought to be important for these drugs to exert their weight-loss effects. They found that activation of GLP-1 receptors in the hindbrain, one of the brain regions studied, was particularly crucial in suppressing food intake. Interestingly, mice with chronic activation of their GLP-1 receptors in the hindbrain did not change how much they ate within a single meal but showed increased latency between meals, indicating that GLP-1 receptors in this brain region are important for increasing satiety (feeling full) after eating.
Next, the study used in vivo two-photon imaging to show that two distinct subpopulations of neurons within the hindbrain are responsible for encoding nutrient-related information vs. aversive information (i.e., nausea). Accordingly, these subpopulations both drive suppression of food intake, but only one does so by inducing nausea. This introduces the possibility of designing a drug that targets one of these subpopulations, which would keep the weight-loss effects and ditch the nausea and vomiting.
Unfortunately, the logistics of a pharmaceutical drug that could target a specific subpopulation of neurons would be pretty tricky. Scientists do it in rodents all the time, but it requires genetic manipulation of the animal. But a breakthrough in drug development is not unheard of – and this type of accomplishment would revolutionize treatment for a whole range of conditions.
Peer Editor: Maria X. Cardenas-Alvarez
