Scientists have discovered the brain’s hidden “off switch” for hunger, and it could revolutionize the fight against obesity. PHOTO/Shutterstock.
By SPECIAL CORRESPONDENT
Scientists have discovered a hidden mechanism in the brain that helps control hunger.
A small protein called MRAP2 was found to act like a guide, helping a key hunger receptor reach the cell surface where it can send stronger “I’m full” signals.
MC4R is a crucial receptor that responds to the peptide hormone MSH and plays a central role in the work of the Collaborative Research Centre 1423, where researchers are studying it in detail both structurally and functionally.
Variations in the MC4R gene are known to be among the most common genetic contributors to severe obesity.
“The knowledge of the 3D structures of the active receptor in interaction with ligands and drugs such as setmelanotide, which we were able to decipher in an earlier study, has enabled us to better understand the new functional data,” says Dr. Patrick Scheerer, project leader at CRC 1423 and co-author of the study, from the Institute of Medical Physics and Biophysics at Charité. Setmelanotide, an approved drug, activates this receptor and specifically reduces feelings of hunger.
“We are proud that CRC 1423 has now also contributed to understanding receptor transport and availability,” says Professor Annette Beck-Sickinger, spokesperson for CRC 1423 and co-author of the study. A total of five projects within the Collaborative Research Centre were involved in this interdisciplinary research.
Through the use of advanced fluorescence microscopy and single-cell imaging, researchers discovered that a protein called MRAP2 plays a key role in shaping how MC4R is positioned and behaves inside cells.
Fluorescent biosensors and confocal imaging revealed that MRAP2 is essential for moving MC4R to the surface of cells, allowing it to more effectively send appetite-suppressing signals.
This discovery reveals an additional layer of control in how hunger is regulated and could inspire new therapies that imitate or adjust MRAP2’s activity to treat obesity and related metabolic diseases.
Professor Heike Biebermann, project leader at CRC 1423 and co-lead author of the study from the Institute of Experimental Pediatric Endocrinology at Charité, notes that this international and interdisciplinary effort combined multiple experimental methods and perspectives to uncover key physiological and pathophysiological insights into appetite regulation with potential clinical impact.
The study’s second co-lead author, Dr. Paolo Annibale, a lecturer in the School of Physics and Astronomy at the University of St Andrews in the UK, says: “This work was an exciting opportunity to apply several microscopy and bioimaging approaches in a physiologically relevant context. In recent years, we have refined this approach to meet the requirements of studying molecular processes in cells.”
This research brought together expertise in live-cell fluorescence microscopy, molecular pharmacology, and structural biology from institutions in Germany, Canada, and the UK, demonstrating the power of interdisciplinary science to uncover new principles of receptor regulation.
