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New drugs that help obese or overweight patients lose weight, such as Ozempic, Wegovy or Mounjaro, and that were initially developed to treat type 2 diabetes because they improve glucose levels and insulin resistance, have been chosen by the Science magazine as the best advance of 2023. Semaglutide – the active ingredient in Ozempic and Wegovy – replicates the action of the human hormone GLP-1, which is released after eating food and generates satiety and stimulates the release of insulin.
Beyond the revolution they represent against overweight, some studies have found that these new slimming drugs also have other health benefits, such as reducing cardiovascular risk or that of some types of cancer. And now, new research has revealed that they also have the potential to act in the brain to reduce inflammation throughout the body. The results, which have been published in Cell Metabolism, have been obtained from tests carried out in animal models in which, beyond weight loss, anti-inflammatory effects were observed.
The new research has been supervised by Dr. Daniel Drucker at the University of Toronto (Canada) and has revealed that these drugs can have a significant impact on the prevention of cardiovascular pathologies, and even neurodegenerative disorders, such as Alzheimer’s and Parkinson’s. that are related to inflammatory processes.
In the new study carried out by Dr. Drucker’s team at the Lunenfeld-Tanenbaum Research Institute (LTRI), which is part of the Sinai Health health system, the relationship between the intake of these drugs and the reduction of the inflammation. Researchers have discovered a gut-brain immune network that controls inflammation throughout the body and influences organ health, a promising finding for understanding and treating metabolic diseases.
A GLP-1-brain-immune axis controls inflammation throughout the body
Dr. Drucker’s early work on the hormone GLP-1 provided an understanding of how it works at a molecular level and has contributed to the development of numerous diabetes medications, including Ozempic. On this occasion, Dr. Drucker focused on finding out how GLP-1 drugs reduce inflammation, which is a common condition in chronic metabolic diseases, since through inflammation the immune system recognizes and eliminates foreign agents such as viruses. and bacteria and promotes healing. However, inflammation can become chronic without an external cause and cause organ damage.
Since immune cells are found in most organs, a logical assumption was that the drugs mitigated inflammation by interacting with GLP-1 receptors on immune cells. This is what happens in the intestine, where GLP-1 activates a large number of immune cells. But in other organs, the number of immune cells with GLP-1 receptors is negligible, indicating that another mechanism is at play.
“Dr. Drucker and his team continue their efforts to explain how these drugs work, and this study deepens our understanding of metabolism and the complex brain-immune network that regulates it.”
“The strange thing is that you can’t find many GLP-1 receptors in all these other organs where GLP-1 seems to work,” says Drucker, who has suggested that the brain could be involved for two reasons: GLP-1 receptors They are abundant in this organ, and the brain and immune system communicate with all the organs of the body.
To conduct the study, postdoctoral researcher Chi Kin Wong induced systemic inflammation in mice by injecting them with a component of the bacterial cell wall or a bacterial substance to induce sepsis, a widespread inflammation that causes organ damage. Surprisingly, GLP-1 agonists decreased inflammation, but only when its receptors in the brain were unblocked. When these brain receptors were pharmacologically inhibited or genetically eliminated in mice, the drugs’ ability to reduce inflammation was lost.
The findings have shown for the first time that there is a GLP-1-brain-immune axis that controls inflammation throughout the body, independent of weight loss, even in peripheral organs devoid of GLP1 receptors, Dr. Drucker said.
Anne-Claude Gingras, director of the LTRI and vice president of research at Sinai Health, has emphasized the impact of the study: “While the scientific community deservedly celebrates GLP-1 agonists and their impact, many unknowns remain. Dr. Drucker and his team have remained tenacious in their efforts to explain how these drugs work, and this study deepens our understanding of metabolism and the complex brain-immune network that regulates it.”
However, further research is needed, and the team is now trying to identify the brain cells that interact with GLP-1. They are also looking at various mouse models of inflammation, including heart disease, atherosclerosis, and inflammation of the liver and kidneys, to determine whether the beneficial effects of GLP-1 in each case are actually mediated by the brain. Understanding how GLP-1 dampens inflammation may open new avenues for reducing complications associated with type 2 diabetes and obesity, Drucker concludes.
