According to one of the researchers, this scientific advance represents “a turning point in the treatment of obesity”.
Spanish scientists have discovered the mechanism through which adipocytesthe cells that mainly make up adipose tissue or body fat, produce leptin, one of the main hormones that regulates appetite, and they have seen that this mechanism also regulates the biological clock of fat cells.
The research, published by the magazine Cell Metabolismhas been led by scientists from the Diabetes and Associated Metabolic Diseases (Diamet) group of the Pere Virgili Health Research Institute (IIPSV), from the Diabetes and Metabolic Diseases Cyber (Ciberdem) and from the Joan XXIII Hospital in Tarragona.
The historical discovery of the leptin as a hormone secreted by adipocytes in the 1990s brought about 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 the fact that numerous scientific papers have 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 correctly, no significant advances had been made on the production process of this hormone in adipose tissue.
This investigation, which has received more than one million euros from the La Caixa Foundation and the State Agency for Investigation of the Ministry of Science and Innovationrepresents, according to the researchers, “a very significant milestone not only from the physiological point of view because it helps to improve the understanding of the biological processes that control body weight, but also to address metabolic diseases such as obesity.”
according to Sonia Fernndez-VeledoIIPSV researcher and Diamet manager: “If everything works correctly, when we eat, leptin levels in the blood increase. This hormone is responsible for sending the satiety signal to our brain. In obese people, more leptin is produced than in the thin ones, 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 the fat in obese people does so excessively,” has added.
The researcher has explained that succinate, an energy metabolite that can also act as a hormone through its receptor SUCNR1has an important role in all these processes.
For many years, a mainly inflammatory role has been attributed to this metabolite, in addition to being identified as a biomarker of metabolic dysfunction in diseases such as obesity and the diabetesbut in recent years, the Diamet group has shown that this is a complex system, since succinate levels also increase in some physiological situations, such as when eating.
“It is in this context that we believe that succinate, through its receptor SUCNR1, naturally regulates energy homeostasis, that is, the internal functions of our body that control a balance between energy intake and expenditure.” Fernndez-Veledo has indicated.
In this study they have shown that one of the mechanisms is through the production of leptin and, therefore, the feeling of satietyand “anticipates that it has other physiological functions acting on other tissues”, according to the researcher.
“In addition, we showed that succinate would determine leptin oscillations throughout the day by controlling the biological clock of adipocytes. In obese people, this mechanism is hyperactivated, which would partly explain the elevated levels of leptin.” leptin”, has specified.
According to Fernández-Veledo, this scientific advance represents “a turning point in the treatment of obesity” and opens the doors to future studies aimed at investigating not only other metabolic functions of succinate, but also at exploring therapies that allow restoring this mechanism and regulate the feeling of satiety
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