Spanish scientists describe a new mechanism regulating leptin, the hormone that stimulates appetite

Spanish researchers describe the role of the succinate metabolite and its relationship with leptin, a hormone that controls the feeling of satiety and a special treatment for the treatment of obesity, a pathology in which this hormonal mechanism is altered.

Scientists from the Diabetes and Associated Metabolic Diseases Research Group (DIAMET), led by the Pere Virgil Institute for Health Research (IIPSV) and associated with the Joan XXIII University Hospital.

Tarracon published the results of his research in the journal Cell Metabolism and managed to discover the mechanism by which adipocytes – the cells that make up most of the adipose tissue or body fat – produce leptin, one of the main hormones. which control the appetite.

“It is also known that this new mechanism controls the biological clock of fat cells. In fact, today it is known that adipocytes have their own internal clock, from the outside as light, which is necessary for the adipose tissue to complete its repair. They explain in the announcement.

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

Since then, and despite the fact that many scientific papers have studied how leptin acts in the central nervous system, inhibiting intake and producing satiety, no significant developments have been made regarding the physiological process of the production of this hormone. .

Sonia Fernández-Veledo, IIPSV researcher and head of DIAMETER: “if everything works correctly, when we eat, the level of leptin in the blood increases. This is the hormone that sends the signal of satiety to our brain. which is produced in thin women, but on the other hand, a phenomenon called leptin resistance arises, which changes the mechanism of satiety.

This research, funded by the La Caixa Foundation and the State Research Agency (Ministry of Science and Innovation), represents a very significant milestone. “Our study not only demonstrates the mechanism by which adipocytes produce leptin, but also why obese people have too much fat,” says Fernandez-Veledo, a mechanism in which succinate is key.

Succinate parts

Succinate is an active metabolite that can also act as a hormone through its receptor SUCNR1, with a role in all these processes very relevant in the context of inflammatory and metabolic diseases, such as obesity and diabetes, in which it is chronically elevated.

For many years, a main inflammatory role has been attributed to it, in addition to being known as a biomarker of metabolic dysfunction. The DIAMETER circle shows that this is a complex system, since succinate levels will also increase in some physiological conditions, such as when we eat.

“We believe that succinate -through its receptor SUCNR1- naturally regulates energy homeostasis, that is, the internal functions of our body, which regulates the balance between energy intake and expenditure. We show that one of the mechanisms is through leptin and production. Therefore, the feeling of satiety, but we anticipate that other it will have physiological functions in other tissues”, I retain this researcher.

“Furthermore, we have shown that succinate determines leptin oscillations throughout the day by regulating the biological clock of adipocytes. In obese humans, this mechanism is hyperactive, which would partially explain elevated leptin levels.”

“The study opens the door to future studies designed not only to investigate other metabolic functions of succinate, but also to investigate therapies that can restore this mechanism, so that its levels, like those of the hormone leptin, can be stabilized and thus recover its role in the feeling of satiety.”

Other institutions participated in the study such as the Center for Biomedical Research in the Network – Diabetes and Metabolic Diseases (CIBERDEM), the CIBER for the Physiopathology of Obesity and Nutrition (CIBEROBN), the Research Centers of Catalonia (CERCA), the University of Rovira and Virgil (URV), the John XXIII University Hospital, Alberto Sols Biomedical Institute, Biomedical Research in Bellvitge (IDIBELL), Sant Pau Biomedical Institute (IBI), Autonomous University of Barcelona (UAB), Biomedical Institute. of Girona (IDIBGI), the University of Girona and the University of Barcelona.

Cell Metabolism 35, 1-19 April 4, 2023