They identify a possible way to avoid the side effects of drugs like Ozempic.

Last year, scientific journals Nature And The science agreed to indicate approval Ozempic (semaglutide) among the most important scientific achievements 2023 yearSix months later, these types of drugs continue to dominate research.

Semaglutide was not the first member of the GLP-1 (glucagon-like peptide-1) family of analogues, but its ability to reduce body weight (to a percentage previously only achievable with bariatric surgery) in addition to controlling diabetes has challenged these goals. Antidiabetic drugs are the focus of treatment for obesity and its associated diseases.

However, you can always look for a better version; An undesirable effect of these revolutionary anti-obesity drugs is nausea and vomiting. research published in the journal Nature This week, scientists identified a pathway in the brain that mediates these side effects.s and open up the possibility of developing effective weight loss drugs that do not cause these side effects.

“We didn’t have a clear idea whether these unpleasant side effects were related to or necessary for the weight loss effect,” explains the lead author. Amber L. Alhadeffneuroscientist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania.

TWO NEURAL CIRCUIT

To find out, they launched a mechanistic study that identified a population neurons in the brain that control food intake without causing nausea in an animal modeland which future and new generation GLP-1 may act on selectively.

Researchers have shown two different neural circuits which generate different effects from the same drug. In the experiment, mice that did not have neurons with GLP-1 receptors in hindbrain or rhombencephalon They were able to eat normally, indicating that the appetite suppressant drug was acting in that area of ​​the brain.

Upon further analysis, they found that the neurons in the hindbrain that mediate satiety and the neurons that mediate food aversion and nausea are different.

Images of hindbrain GLP1 receptor neurons taken in living mice showed that most neurons respond to either nourishing or aversive stimuli, but not both. What’s more, the study found that GLP1 neurons in a part of the hindbrain called the area postrema respond more to aversive stimuli (and cause nausea), while GLP1 neurons in another area called the nucleus solitarius, or nucleus abdominis, respond to food stimuli. .

Working with both groups of neurons separately, the researchers found that activation of neurons in nucleus of the solitary tract induces satiation without aversive behavior, while activation of neurons in Postal zone causes a strong negative reaction.

Drugs always reduced food intake even when the path of disgust was suppressed to food and nausea, so the researchers concluded that the population of neurons in the nucleus of the solitary tract could serve as a target for future anti-obesity drugs that reduce food intake without nausea.

DRUGS WITHOUT SIDE EFFECTS

“If there was a way to activate just the GLP-1 receptor neurons in the solitary tract nucleus or all the other GLP-1 receptor neurons while avoiding just the neurons in the area postrema, that would certainly be a much better drug,” he said. Nature Alhadef: “The main thing, of course, is how to do it.”

In fact, the authors believe that the concept of separating therapeutic effects from secondary effects at the level of neural circuits could theoretically apply to other drugs“Given that nausea and vomiting are side effects of thousands of treatments for human diseases, this concept could be applied to the study of treatments beyond those used to treat obesity, with the goal of developing drugs that better target the mechanisms that reverse the pathologies and alleviate the symptoms of obesity disease, but avoid the negative side effects.”