This tiny protein helps control how hungry you feel

In a study published in Science Signaling on December 16, an international research team led by scientists at the University of Birmingham examined how a helper protein known as MRAP2 supports an appetite regulating protein called MC3R. MC3R plays a key role in deciding whether the body stores energy or uses it.

Building on earlier hunger research

Previous studies had already shown that MRAP2 is essential for the activity of a related protein (MC4R), which is known to control hunger. The new research set out to determine whether MRAP2 provides the same kind of support for the closely related protein MC4R.

To explore this question, the researchers used cell models to observe how the proteins interact. They found that when MRAP2 was present in equal amounts with MC3R, cellular signaling became stronger. This result suggests that MRAP2 helps MC3R do its job of balancing energy intake with energy use. The team also identified specific regions of MRAP2 that are required for supporting signaling through both MC3R and MC4R.

How genetic mutations weaken appetite signals

The researchers then investigated what happens when MRAP2 carries genetic mutations that have been identified in some people with obesity. In these experiments, mutated versions of the supporter protein (MRAP2) failed to boost MC3R signaling. As a result, the appetite regulating protein did not respond as effectively.

These findings indicate that changes in MRAP2 can interfere with the hormone system that normally helps maintain energy balance. When this system does not work as intended, appetite regulation may be disrupted.

New clues for obesity risk and future treatments

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."

By learning more about how MRAP2 supports appetite related signaling, researchers hope to determine whether future drugs could target this protein. Such treatments might strengthen feelings of fullness, reduce overeating, and improve the body's overall energy balance, offering new options for weight loss when dieting alone is not effective.

A collaborative effort in metabolism and cell signaling research

The research was carried out by a team from the Department of Metabolism and Systems Science and the Centre of Membrane Proteins and Receptors (COMPARE). COMPARE is a cross-University Research Centre involving the Universities of Birmingham and Nottingham, focused on studying how cells communicate in both health and disease. Its goal is to develop new therapies for widespread conditions such as cardiovascular disease, diabetes, and cancer. The center is supported by advanced research facilities, including the COMPARE Advanced Imaging Facility, which is available to researchers from academia and industry.