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New target for obesity treatment discovered

23/10/2023
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A study published in the journal Biofactors has revealed promising results regarding the activation of the angiotensin II type 2 receptor (AT2R) in brown adipose tissue, providing a new pathway for the treatment of obesity. The article, titled ‘Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity’, has been published in the renowned scientific journal Biofactors. Developed and led by researchers from the Metabolism and Vascular Function Group (MET-VASC), the study is part of the doctoral thesis of researcher Fabiola Álvarez Gallego. It was a collaborative effort with the ‘Nemesio Díaz’ Institute of Advanced Molecular Medicine (IMMA) at Universidad CEU San Pablo and the Universidad de Cádiz.

According to data from the 2020 European Health Survey in Spain, 44.9% of men and 30.6% of women are overweight, and 16.5% of men and 15.5% of women suffer from obesity. These numbers are highly relevant as both conditions are significant risk factors for some of the chronic diseases that are a leading cause of death worldwide, such as heart attacks, strokes, or even some types of cancer. The results of this study provide a new approach to the mechanisms underlying the activation of brown adipose tissue and its relationship with obesity. Furthermore, they suggest that AT2R activation could be a safe and effective therapeutic strategy for treating obesity and its metabolic and cardiovascular complications while minimizing the adverse effects associated with other therapeutic approaches.

The experiment was conducted on mice that were fed a high-fat diet for six weeks. Half of the animals were treated with compound 21 (C21), a selective agonist of the AT2R receptor. The treated animals showed an increase in brown adipose tissue mass compared to animals on the same diet who did not receive the treatment. Additionally, they exhibited greater thermogenic capacity, as well as a reduction in inflammatory and oxidative markers.

Fabiola Álvarez, the  lead author of the study and a researcher in training at the CEU International Doctoral School (CEINDO), explained, "In previous research, we had already discovered that AT2R activation with a drug called Compound 21 protects vascular function in the aorta of obese animals. Now, our new findings support the idea that AT2R activation may be a promising strategy in the treatment of obesity and its complications. By increasing the mass and activity of brown adipose tissue, we can improve energy metabolism, which could help counteract the negative effects of obesity on the cardiovascular system and glycemic control."

The activation of brown adipose tissue as a strategy for metabolic diseases has gained significant attention in recent years. According to Martín Alcalá, the principal investigator of the project funded by the Ministry of Science and Innovation, "While white adipose tissue is an organ for fat storage, brown adipose tissue is an organ that has the ability to burn energy substrates such as glucose or fatty acids, dissipating the resulting energy as heat, making it a 'calorie-burning' organ. However, individuals with obesity have a lower amount of this tissue and lose their  ability to activate it, so finding new ways to restore its function would provide a new therapeutic tool against this disease." 

The importance of finding new activation pathways lies in the fact that the main therapies used to enhance the thermogenic capacity of this tissue,  although they increase calorie expenditure, have significant cardiovascular side effects. However, this new approach not only avoids the risk of cardiovascular accidents but also plays a protective role, which is especially crucial in obese patients whose primary cause of associated death is strokes and heart attacks.

More information:

Álvarez-Gallego F, González-Blázquez R, Gil-Ortega M, Somoza B, Calderón-Dominguez M, Moratinos J, et al. Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity. Biofactors. 2023. doi: 10.1002/biof.1981
Palabras clave Obesity Cardiovascular diseases Investigation Health