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Satiety’s little helper: protein that supports appetite regulating-protein identified

Mutated versions of MRAP2 protein, seen in some people predisposed to obesity, did not see enhanced signalling seen in healthy individuals

16 December 2025
Picture of several plates of food

A protein essential to the human body for managing energy and regulating appetite relies on a partner protein, according to new research, and the findings could help researchers better understand genetic obesity.

In a paper published in Science Signalling, an international research team led by academics from the University of Birmingham, looked at the supporting role of a partner protein called MRAP2 with an appetite regulating protein called MC3R, which coordinates whether the body stores energy or burns it.

Previous studies have shown that MRAP2 plays a key supporting role for a similar protein (MC4R), which controls hunger, and this latest study attempted to discover whether MRAP2 worked in the same way for the structurally similar protein MC4R.

The identification of this protein, MRAP2, as a key aide or supporter to these essential appetite-regulating proteins also gives us new clues for people who have a genetic predisposition to obesity

Dr Caroline Gorvin, Associate Professor and lead author of the study

Using cell models, the team found that the presence of the MRAP2 protein, in a 1:1 ratio with MC3R, improved cellular signalling. The findings suggest that this supporting protein may help MC3R perform its role in balancing energy intake and energy use. The team also identified critical parts of MRAP2 that are needed to accomplish its role in aiding both MC3R and MC4R signalling.

Further analysis looked at whether the same enhanced signalling action was seen with MRAP2 with genetic mutations seen in some people with obesity. The team found that when mutated supporter proteins (MRAP2) were introduced to MC3R, there was no enhanced signalling of the appetite regulating protein. The findings suggest that mutations in the MRAP2 protein contribute to reducing the normal functioning of the hormone system that regulates energy balance.

Dr Caroline Gorvin, Associate Professor at the University of Birmingham and lead author of the study, said: “The findings give us some important insights into what’s going on in the hormonal system, related to some key functions like energy balance, appetite, and puberty timing.

“The identification of this protein, MRAP2, as a key aide or supporter to these essential appetite-regulating proteins also gives us new clues for people who have a genetic predisposition to obesity, and how MRAP2 mutations are a clear indication of risk.”

Diagram of cells with proteins moving around them

Microscopy image showing cells expressing MC3R (magenta) exposed to agonist. After 30 minutes MC3R should internalise (move away from cells surface) to Rab5 positive endosomes (seen as white dots in merge and some highlighted with arrows). In cells co-expressing MRAP2, MC3R internalisation is reduced (fewer white dots), which means MC3R is at the cell surface for longer and can initiate more signalling.

Understanding the tools that MRAP2 uses to aid signalling will help researchers determine whether drugs targeting MRAP2 could boost its ability to help modulate MC3R and MC4R. These drugs could enhance feelings of fullness, reduce overeating and improve the body’s energy balance to help with weight loss that isn’t manageable with dieting alone.

The research was conducted by a team from the Department of Metabolism and Systems Science and the Centre of Membrane Proteins and Receptors (COMPARE). COMPARE is a unique cross-University Research Centre between the Universities of Birmingham and Nottingham aimed at investigating the mechanisms of cell communication in physiology and disease to develop innovative therapies for common conditions such as cardiovascular disease, diabetes or cancer. COMPARE is supported by dedicated, state-of-the-art facilities, including the COMPARE Advanced Imaging Facility, which is open to internal and external researchers from both academia and industry.

Notes for editors

  • For media enquiries please contact Tim Mayo, Press Office, University of Birmingham, tel: +44 (0)7815 607 157.
  • Full paper reference: Jalamuddin, A., et al, 2025, The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling, Science Signaling, DOI: 10.1126/scisignal.adu4315
  • The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, educators and more than 40,000 students from over 150 countries.
  • England’s first civic university, the University of Birmingham is proud to be rooted in of one of the most dynamic and diverse cities in the country. A member of the Russell Group and a founding member of the Universitas 21 global network of research universities, the University of Birmingham has been changing the way the world works for more than a century.
  • The University of Birmingham is a founding member of Birmingham Health Partners (BHP), a strategic alliance which transcends organisational boundaries to rapidly translate healthcare research findings into new diagnostics, drugs and devices for patients. Birmingham Health Partners is a strategic alliance between nine organisations who collaborate to bring healthcare innovations through to clinical application:
    • University of Birmingham
    • University Hospitals Birmingham NHS Foundation Trust
    • Birmingham Women's and Children's Hospitals NHS Foundation Trust
    • Aston University
    • The Royal Orthopaedic Hospital NHS Foundation Trust
    • Sandwell and West Birmingham Hospitals NHS Trust
    • Health Innovation West Midlands
    • Birmingham and Solihull Mental Health NHS Foundation Trust
    • Birmingham Community Healthcare NHS Foundation Trust

Featured staff

  • Dr Caroline Gorvin

    Sir Henry Dale Fellow

    Staff Profile for Dr Caroline Gorvin, Sir Henry Dale Fellow and Associate Professor of Receptor Biology in the Department of Metabolism and Systems Science, University of Birmingham.

    Phone: +44 (0)121 414 6857
    Email:

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