The Diabetes and Associated Metabolic Diseases (DIAMET) research group, from the Pere Virgili Health Research Institute (Iipsv) and linked to the Joan XXIII University Hospital of Tarragona, has 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. In addition, he has identified that this mechanism regulates the biological clock of fat cells.
The research, published in the Cell Metabolism magazine, has received more than one million euros from the La Caixa Foundation and the State Research Agency, according to the foundation in a statement in which it recalled that today it is known that Adipocytes have "their own internal clock", independent of external factors such as light, "essential for adipose tissue to perform its functions correctly".
At this point, the foundation recalled that the "historical" discovery in the 1990s of leptin as a hormone secreted by adipocytes was "a paradigm shift" by demonstrating that body fat should be considered "an active endocrine organ that regulates appetite and body weight. Since then, despite the fact that "numerous" works have studied how leptin acts in the central nervous system, inhibiting intake by producing a feeling of satiety and why in people with obesity this mechanism "does not work correctly", in his opinion it does not “significant advances” had been made on the production process of this hormone in adipose tissue.
In this sense, it was defended that the new research represents "a very significant milestone" not only from the physiological point of view, since "it helps to improve the understanding of the biological processes that control body weight", but also for the approach metabolic diseases such as obesity.
In this regard, the Iipsv researcher and Diamet manager, Sonia Fernández-Veledo, pointed out that "if everything works correctly, when we eat, leptin levels in the blood increase" and that this hormone is "responsible for sending the satiety signal to our brain." "In obese people, 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," he stated, to indicate That is why obese people have an "altered" satiety mechanism.
The foundation added that succinate, an energy metabolite that can also act as a hormone through its Sucnr1 receptor, has a "very relevant role in all these processes" and added that the Diamet group is an "international benchmark" in the study of this metabolite in the context of inflammatory and metabolic diseases, such as obesity and diabetes.
According to Fernández-Veledo, it is in this context that experts believe that succinate, through its receptor, "naturally regulates" energy homeostasis, that is, the internal functions of the organism that "control that there is a balance between the intake and energy expenditure.
“In this study we show that one of the mechanisms is through the production of leptin and, therefore, the feeling of satiety, but we anticipate that it will have other physiological functions acting in other tissues. In addition, we demonstrated that succinate would determine leptin oscillations throughout the day by controlling the biological clock of adipocytes", she added, convinced that in people with obesity, this mechanism "is hyperactivated", which, his understanding, "would explain, in part, the elevated leptin levels."
For the foundation, 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 "exploring therapies that allow restoring this mechanism". This would ensure that their levels, as well as those of the hormone leptin, "can be stabilized and can thus recover their role in regulating the feeling of satiety", according to the expert.
