They discover a key mechanism for the formation of brown adipose tissue that prevents obesity

Obesity is a growing global health problem, the prevalence of which has tripled since 1975. Currently, it affects 650 million people worldwide, and in countries such as Spain the incidence among adults is 28%. This pathology is related to cardiovascular diseases, type 2 diabetes, osteoarthritis and certain forms of cancer.

The person in charge of managing the body’s fat reserve is the adipose tissue, and there are two different types: white adipose tissue, which stores energy reserves in the form of lipids, and brown adipose tissue, responsible for the oxidation of lipids to generate heat .

Now, a team of scientists has described a mechanism that regulates the correct formation of brown adipose tissue through a natural process of cell renewal: autophagy. In the investigation, the team verified how the NCOR1 protein (regulator of several genes) needs to be degraded by autophagy so that the cells of brown adipose tissue develop normally.

The study was led by Antonio Zorzano, professor at the Department of Biochemistry and Molecular Biomedicine at the Faculty of Biology at the University of Barcelona (UB), head of the Complex Metabolic Diseases and Mitochondria Laboratory at the Institute for Research in Biomedicine (IRB Barcelona). ), and group leader of the Center for Biomedical Research Network of Diabetes and Associated Metabolic Diseases (CIBERDEM), in Spain.

The protein responsible for marking NCOR1 for elimination is TP53INP2, which has been the object of study for years at the Complex Metabolic Diseases and Mitochondria Laboratory at IRB Barcelona.

Using mouse animal models, researchers have also found that defective or insufficient adipose tissue (removal of TP53INP2 causes an error in the degradation of NCOR1) is associated with higher levels of obesity.

‘There is a clear correlation between low levels of brown adipose tissue and obesity, but we still don’t know if obesity is the cause and consequence. Our discovery opens the way to intervene in autophagy processes to reinforce this brown adipose tissue and thus prevent or treat obesity and other associated metabolic diseases”, explains Zorzano.

The team has described a mechanism that regulates the correct formation of brown adipose tissue through a natural process of cell renewal: autophagy. (Photo: UB)

Autophagy as a regulatory tool

Autophagy is a natural process of degradation of cellular components. Initially it was believed that it responded mainly to cleaning of damaged or aged cellular elements. However, for some years scientific evidence has pointed to it as a key element in the regulation of cellular functions by eliminating proteins that perform specific functions.

The study links autophagy and obesity through the development of brown adipose tissue. “In a previous study we had also observed that the TP53INP2 protein has the opposite effect on the formation of white adipose tissue; that is, it represses its formation. This makes this protein an ally for a healthier management of fats as it promotes their oxidation and at the same time prevents their accumulation”, explains Alba Sabaté, postdoctoral researcher at the Complex Metabolic Diseases and Mitochondria Laboratory at IRB Barcelona and first author of the study.

The work has been carried out in collaboration with research groups from the Faculty of Medicine and Health Sciences of the UB, the Vall d’Hebron Research Institute in Barcelona and the University of Cambridge (United Kingdom), among other institutions. .

The study is titled “Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis.” And it has been published in the academic journal Autophagy. (Source: UB)