WASHINGTON DC: Researchers have identified a previously overlooked protein that plays a crucial role in regulating appetite and energy use in the body. This “helper” protein, known as MRAP2, supports a key system that determines whether the body burns energy or stores it. When this protein does not function properly, appetite signals can weaken, leading to potential imbalances.
New research suggests that the body relies on this protein to manage appetite and energy levels, but it cannot function independently. Instead, MRAP2 depends on a partner protein, MC3R, to work effectively. This groundbreaking discovery could help scientists better understand how genetic factors contribute to obesity.
Unveiling the Role of MRAP2 in Appetite Regulation
In a study published in Science Signalling on December 16, an international research team led by scientists at the University of Birmingham examined how 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 previous studies, researchers had already shown that MRAP2 is essential for the activity of a related protein, MC4R, known to control hunger. The new research aimed to determine whether MRAP2 provides similar support for MC3R.
Exploring Protein Interactions
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 required for supporting signaling through both MC3R and MC4R.
Genetic Mutations and Appetite Signals
The researchers then investigated what happens when MRAP2 carries genetic mutations identified in some people with obesity. In these experiments, mutated versions of MRAP2 failed to boost MC3R signaling, resulting in the appetite-regulating protein not responding 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.
“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,” said Dr. Caroline Gorvin, Associate Professor at the University of Birmingham and lead author of the study.
Implications for Obesity Risk and Future Treatments
The identification of MRAP2 as a key aide to essential appetite-regulating proteins provides new clues for individuals with a genetic predisposition to obesity. Understanding how MRAP2 mutations indicate risk is a significant step forward.
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 conducted 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 center involving the Universities of Birmingham and Nottingham, focused on studying how cells communicate in both health and disease.
Supported by advanced research facilities, including the COMPARE Advanced Imaging Facility, the center aims to develop new therapies for widespread conditions such as cardiovascular disease, diabetes, and cancer. The collaborative effort underscores the importance of interdisciplinary research in tackling complex health challenges.
