According to one of the researchers, this scientific advance represents “a turning point in the treatment of obesity”.

Spanish scientists discovered the mechanism by which adipocytesthe cells that make up mainly adipose tissue or body fat, produce the leptinone of the main hormones that regulate appetiteand saw that this mechanism also regulates the biological clock of fat cells.

The research, published by the journal cellular metabolismIt was led by scientists from the Diabetes and Associated Metabolic Diseases (Diamet) group at the Pere Virgili Health Research Institute (IIPSV), the Diabetes and Metabolic Diseases Cyber​​(Ciberdem) and the Joan XXIII Hospital in Tarragona.

The historic discovery of leptin as a hormone secreted by adipocytes in the 1990s represented a paradigm shift by showing that body fat should be considered an active endocrine organ that regulates appetite and body weight.

Since then, and despite numerous scientific works having studied how leptin acts on the central nervous system (inhibiting intake by producing the feeling of satiety) and why in people with obesity this mechanism does not work correctlythere were no significant advances in the production process of this hormone in adipose tissue.

This research, which received more than one million euros from the La Caixa Foundation and the State Research Agency of the Ministry of Science and Innovationrepresents, according to the researchers, “a very significant milestone, not only from a physiological point of view because it helps to improve the understanding of the biological processes that control body weight, but also in the fight against metabolic diseases such as obesity”.

According to Sonia Fernandez-Veledoresearcher at IIPSV and manager of Diamet: “If everything goes well, when we eat, the levels of leptin in the blood increase. This hormone is responsible for sending the satiety signal to our brain. , but in turn, a phenomenon known as leptin resistance develops, which means that the body does not respond to this hormone.

“People with obesity therefore have an altered satiety mechanism. Our study not only demonstrates the mechanism by which adipocytes produce leptin, but also why fat in obese people does so excessively,” he added.

The researcher explained that succinate, an energetic metabolite that can also act as a hormone through its receptor SUCNR1plays an important role in all these processes.

For many years, this metabolite was attributed a mainly inflammatory role, in addition to identifying it as a biomarker of metabolic dysfunctions in diseases such as obesity and the diabetesbut in recent years, the Diamet group has shown that this is a complex system, as succinate levels also increase in some physiological situations, such as eating.

“It is in this context that we believe that succinate, through its SUCNR1 receptor, naturally regulates energy homeostasis, that is, the internal functions of our body that control the balance between energy intake and expenditure,” said Fernández-Veledo .

In this study they showed that one of the mechanisms is through the production of leptin and, therefore, the feeling fulland “anticipates that it has other physiological functions acting in other tissues”, according to the researcher.

“In addition, we showed that succinate would determine leptin oscillations throughout the day, controlling the biological clock of adipocytes. In people with obesity, this mechanism is hyperactivated, which would partly explain the high levels of leptin”, he specified.

According to Fernández-Veledo, this scientific advance represents “a turning point in the treatment of obesity” and opens the door to future studies that aim to investigate not only other metabolic functions of succinate, but also to explore therapies that allow to restore this mechanism and regulate the sensation of satiety.

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