They discover a mechanism that regulates the biological clock and the feeling of satiety

A new mechanism has been discovered that regulates the biological clock and the hormone that controls the feeling of satiety. Specifically, a new study has revealed 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 the feeling of satiety.

The historical discovery of leptin as a hormone secreted by adipocytes in the 1990s was a paradigm shift since it revealed that body fat should be considered an active endocrine organ that regulates the sensation of satiety and body weight. Since then, and although numerous scientific papers have studied how leptin acts in the central nervous system (inhibiting food intake by producing a feeling of satiety) and why this mechanism does not work correctly in obese people, no advances have been made. significant in terms of the production process of this hormone in adipose tissue.

The new research, carried out by a team headed by Teresa Villanueva-Carmona, from the Pere Virgili Health Research Institute (IIPSV), constitutes a highly significant milestone not only from the physiological point of view (since it improves the understanding of the biological processes that control body weight), but also from the point of view of addressing metabolic diseases such as obesity.

The work has been led by the Diabetes and Associated Metabolic Diseases Research Group (DIAMET), of the Pere Virgili Health Research Institute (IIPSV) and linked to the Joan XXIII University Hospital of Tarragona. A research group from the Rovira i Virgili University (URV) in Tarragona has also participated.

In the words of Sonia Fernández-Veledo, head of the DIAMET group: «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. The researcher points out that, in the case of obese people, more leptin is produced than in those who are thin, but at the same time, the phenomenon known as leptin resistance occurs, which means that the body does not respond to that 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,” she explains.

Lídia Cedó Giné, Teresa Villanueva Carmona, Sonia Fernández-Veledo and Joan Vendrell, from the research team. (Photo: URV)

According to the World Health Organization (WHO), more than one billion people worldwide are obese, a figure that continues to rise. Obesity –WHO warns– is directly associated with type 2 diabetes, cardiovascular diseases and those related to mental health, hypertension, stroke and various forms of cancer.

Succinate, key in this process

Succinate, an energy metabolite that also acts as a hormone through its receptor SUCNR1, plays a very important role in all these processes. 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). 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 (in these types of patients its levels are chronically elevated). However, in recent years, the DIAMET group has shown that this is a complex system, since succinate levels also increase (although transiently) in some physiological situations, such as when we eat food.

As Sonia Fernández-Veledo points out: «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 organism that control that there is a balance between the intake and energy expenditure. The study shows 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 on other tissues. In addition, we demonstrated 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 partly explain the high levels of leptin,” says the researcher.

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, thus achieving that its levels, as well like those of the hormone leptin, can be stabilized and recover their role in regulating the feeling of satiety.

The study is titled “SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression”. And it has been published in the academic journal Cell Metabolism. (Source: URV)