A research effort that brought together specialists from Germany, Canada, and the United Kingdom has identified an unknown mechanism in the brain that regulates the sensation of hunger. The discovery opens up new avenues in the treatment of obesity.
An international team of scientists has identified the role of a small protein, called MRAP2, which acts as a „guide” for an important appetite receptor, MC4R. This protein helps the receptor reach the cell surface, where it can transmit stronger signals to the brain that the body is full.
The MC4R receptor (melanocortin-4) plays an essential role in appetite regulation and responds to the hormone MSH (melanocortin). Its genetic variant is one of the most common hereditary causes of severe obesity.
Within the Collaborative Research Centre 1423 (CRC 1423) in Germany, scientists have closely analyzed the structure and function of this receptor.
„Understanding the three-dimensional structure of the active receptor, analyzed in interaction with ligands (molecules that bind to the receptor) and with drugs such as setmelanotide, has allowed us to interpret more accurately how the receptor functions and responds to stimulation,” explained Dr. Patrick Scheerer, project coordinator at the Institute of Medical Physics and Biophysics at Charité in Berlin.
Setmelanotide is an approved drug that activates the MC4R receptor and reduces the sensation of hunger in patients with specific genetic mutations.
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### A New Approach to Treating Obesity
The team led by Prof. Annette Beck-Sickinger from CRC 1423 involved five interdisciplinary projects that contributed to deciphering how the receptor is transported and activated.
Using advanced fluorescence microscopy and single-cell imaging, researchers have found that MRAP2 determines how the MC4R receptor is positioned inside cells. This protein is essential for transporting the receptor to the cell surface, where it can transmit signals that inhibit hunger.
The discovery provides a new perspective on the physiological control of appetite and could inspire the development of new therapies that mimic or regulate MRAP2 activity for the treatment of obesity and associated metabolic diseases.
„This international collaboration, which combined various experimental methods and complementary perspectives, has led to a deeper understanding of appetite regulation mechanisms,” emphasized Prof. Heike Biebermann, study co-author and researcher at the Experimental Pediatric Endocrinology Institute at Charité.
The study, involving researchers from Charité – Universitätsmedizin Berlin, in collaboration with the University of Leipzig and the University of St Andrews, was recently published in the journal Nature Communications.