Encephalic trunk neurons are kept for the effects of semaglutid weight loss

Summary: Researchers have identified a specific group of brain trunk neurons that mediate appetite reduction and the weight loss effects of the semaglutida without triggering side effects such as nausea. In mice, the activation of these neurons led to a reduction in food intake and fat loss, imitating the benefits of medication.

On the contrary, disabled them decreased the effects of the semagglutide on the weight, but not on its adverse symptoms. This discovery could lead to more specific obesity treatments that preserve the benefits of GLP-1R agonists while minimizing discomfort.

Key facts:

Specific neurons: a specific set of neurons in the dorsal vagal complex mediating the effects that suppress the appetite of the semaglutida.

Source: Gothenburg University

A specific group of nerve cells in the brain stem seems to control how the semaglutida affects appetite and weight, without causing nausea.

The discovery, made at the University of Gothenburg, could pave the way for better drugs to treat obesity.

The semaglutida belongs to a group of drugs called GLP-1R agonists and it has been shown to effectively reduce food intake and body weight. The medicine is already well established as part of the treatment for obesity and type 2 diabetes, but can cause side effects such as nausea and muscle loss.

In a new study, researchers at the Sahlgrenska Academy of the University of Gothenburg have shown that it is possible to distinguish nerve cells in the brain that control the beneficial effects, such as the reduction of food intake and the loss of fat, of which they contribute to side effects.

The study is published in Cell Metabolism magazine.

Activated nerve cells

To investigate how the semaglutida affects the brain, the researchers worked with mice. They traced which nerve cells were activated by the drug and then could stimulate these cells, without administering the drug itself.

The result was that the mice ate less and lost weight, as they did when they treated with semaglutida. When these nerve cells were killed, the effect of the drug on appetite and fat loss, on the other hand, decreased significantly. However, side effects such as nausea and muscle loss remained.

“This suggests that these nerve cells control the beneficial effects of semaglutida. Therefore, we have identified a specific group of nerve cells that is necessary for the effects that the semaglutida has on weight and appetite, but that does not seem to contribute to any significant extent to side effects such as nausea.

“If we can point to the treatment there, we can maintain the positive effects while reducing the side effects,” says Júia Teixidor-Deulofeu, first author of the study and doctoral student at the Sahlgrenska Academy of the University of Gothenburg.

The effect on the brain

The identified nerve cells are found in an area of ​​the brain called dorsal vagal complex. For researchers, the result is not only an early step towards potentially improved treatment, but also provides new knowledge about how the semagglutide works in the brain.

The study also provides a deeper vision of how the brain trunk regulates our energy balance.

“Currently, semaglutidas and other GLP-1R agonists are prescribed to more and more people and are also being investigated for other potential indications such as use disorders of neurodegenerative substances and diseases.

“It is important to understand how these drugs really work. The better we understand this, the greater the opportunity we have to improve them,” says Linda Engström Ruud, a researcher and supervisor of doctoral students Júlia Teixidor-Deulofeu and Sebastian Bid Sköldheden, both worked on the project.

On this Semaglutida and Neuroscience Research News

Author: Julia Teixidor-Deulofeu
Source: Gothenburg University
Contact: Júia Teixidor-Deulofe-University of Gothenburg
Image: The image is accredited to Neuroscience News

Original research: open access.
“The semaglutid effects on the energy balance are mediated by the neurons ADCYAP1+ in the dorsal vagal complex” by Júlia Teixidor-Deulofeu et al. Cell metabolism

Abstract

The semaglutid effects on the energy balance are mediated by ADCYAP1+ neurons in the dorsal vagal complex

The use of the GLP-1R agonist semaglutida is revolutionizing the treatment of obesity, however, its mechanistic effects on energy balance are still difficult to achieve.

Here, we demonstrate that the reactivation of the neurons of the semaglutid -sensitive vagal complex imitates the effects of the drug of reducing food intake and body weight and promoting the use of fats and the aversion to the conditioned taste.

We observe that many of the neurons of the area activated by semaglutida (AP) and the nucleus of the solitary neurons of the tract (NTS) express ADCYAP1 mRNA, and the ablation of the AP/NTS neurons Adcyap1+ largely reverses the effects of semaglutida in the energy balance in an acute way in the obese mice.

AP/NTS AP/NTS neurons activated by semaglutida promote fat loss instead of lean mass, with only a modest effect on aversion to conditioned taste.

In addition, the NTS adcyap1+ neurons are dedicated to the AP neurons that express LPG-1R and are necessary for the active-induced activation of several structures related to the satiety downstream.

The selective orientation of adcyop1+ neurons sensitive to semaglutida has potential to improve future antiobesity treatments.