Researchers Identify Key Protein Regulating Appetite and Weight.pdf

Researchers at Leipzig University and Charité – Universitätsmedizin Berlin have identified a key mechanism showing how the MRAP2 protein regulates appetite and body weight.

1. Researchers Identify Key Protein
Regulating Appetite and Weight

​​Source: medicalxpress.com
Key Points:
●​MRAP2 controls appetite via MC4R.
●​Target for obesity treatment.
●​International research breakthrough.
Berlin, Oct. 6—Researchers at Leipzig University and Charité – Universitätsmedizin
Berlin have identified a key mechanism showing how the MRAP2 protein regulates
appetite and body weight. The discovery explains how a protein called MRAP2
(melanocortin 2 receptor accessory protein 2) influences another brain receptor, MC4R
(melanocortin-4 receptor), which plays a central role in controlling appetite and energy
balance. The findings were published in Nature Communications. The study was conducted under the Collaborative Research Centre (CRC) 1423 –
Structural Dynamics of GPCR Activation and Signaling. Scientists found that MRAP2

2. directly affects how MC4R functions and is transported within cells, providing new
insights into how the body regulates food intake. This discovery explains in detail how
the MRAP2 protein regulates appetite.
MC4R is a receptor activated by the hormone MSH, which signals the brain to reduce
hunger. Mutations in MC4R are among the most common genetic causes of severe
obesity. Researchers say understanding how this receptor works could lead to better
treatments for metabolic disorders.
“The knowledge of the 3D structures of the active receptor in interaction with ligands
and drugs such as setmelanotide, which we deciphered in an earlier study, has enabled
us to better understand the new functional data,” said Dr. Patrick Scheerer, project
leader at CRC 1423 and co-author of the study from Charité’s Institute of Medical
Physics and Biophysics.
Setmelanotide, an approved drug, activates MC4R and reduces feelings of hunger. “We
are proud that CRC 1423 has now also contributed to understanding receptor transport
and availability,” said Professor Annette Beck-Sickinger, spokesperson for CRC 1423 and
co-author from Leipzig University. Five projects within the centre collaborated on this
interdisciplinary research.
Protein found essential for receptor activity
Using modern fluorescence microscopy and single-cell imaging, the team showed that
MRAP2 is essential for transporting MC4R to the cell surface, where it can effectively
transmit appetite-suppressing signals. Without MRAP2, MC4R remains trapped inside
the cell, reducing its ability to communicate with hormones that regulate hunger.
Fluorescent biosensors and confocal imaging revealed how the MRAP2 protein
regulates appetite by altering MC4R’s localization and behaviour, uncovering a new
level of control over appetite-related signaling. These insights open the door to
therapeutic strategies that could mimic or enhance MRAP2’s function, offering
potential treatments for obesity and related conditions.
Collaboration drives scientific insight
“This interdisciplinary and international collaboration enabled researchers, using
different approaches and experimental methods, to uncover important physiological

3. and pathophysiological aspects of appetite regulation with therapeutic relevance,” said
Professor Heike Biebermann, project leader at CRC 1423 and co-lead author from
Charité’s Institute of Experimental Pediatric Endocrinology.
Co-lead author Dr. Paolo Annibale, a lecturer at the University of St Andrews in the
United Kingdom, said the project allowed scientists to apply advanced microscopy and
bioimaging techniques in a physiologically relevant context. “In recent years, we have
refined this approach to study molecular processes in cells,” he said.
The research brought together experts in live-cell fluorescence microscopy, molecular
pharmacology, and structural biology from Germany, Canada, and the UK. According to
the authors, the collaboration highlights how combining multiple scientific disciplines
can reveal new principles of receptor regulation and advance the understanding of metabolic health, showing again how the MRAP2 protein regulates appetite.
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