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Spanish scientists have discovered the mechanism through which adipocytes, the cells that mainly make up adipose tissue or body fat, produce leptin, one of the main hormones that regulates appetite, and have seen that this mechanism also regulates the biological clock of fat cells.
The research, published in the journal Cell Metabolism, has been led by scientists from the Diabetes and Associated Metabolic Diseases (Diamet) group of the Pere Virgili Health Research Institute (IIPSV), the Ciber de Diabetes y Enfermedades Metabolicas (Ciberdem) and the Joan XXIII Hospital in Tarragona.
The historic discovery of leptin as a hormone secreted by adipocytes in the 1990s marked 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 works have studied how leptin acts in the central nervous system (inhibiting intake by producing the feeling of satiety) and why in people with obesity this mechanism does not work properly, no significant advances had been made on the production process of this hormone in adipose tissue.
This research, which has received more than one million euros from the La Caixa Foundation and the State Research Agency of the Ministry of Science and Innovation, represents, 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."
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According to Sonia Fernández-Veledo, IIPSV researcher and head of Diamet: "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 people with obesity, more leptin is produced than in thin people, but, in turn, a phenomenon known as leptin resistance develops, which means that the body does not respond to this hormone."
"People with obesity have, therefore, the mechanism of satiety altered. Our study not only demonstrates the mechanism by which adipocytes produce leptin, but also why fat from people with obesity does so excessively."
The researcher explained that succinate, an energy metabolite that can also act as a hormone through its SUCNR1 receptor, has a relevant role in all these processes.
For many years this metabolite has been attributed a mainly inflammatory role, in addition to identifying it as a biomarker of metabolic dysfunction in diseases such as obesity and diabetes, but in recent years, the Diamet group has shown that this is a complex system, since succinate levels also increase in some physiological situations, like when eating.
"It is in this context where 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," said Fernández-Veledo.
In this study they have shown that one of the mechanisms is through the production of leptin and, therefore, the feeling of satiety, and "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 people with obesity, this mechanism is hyperactivated, which would explain, in part, the elevated levels of leptin."
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 to explore therapies that allow restoring this mechanism and regulating the feeling of satiety.
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