Researchers identify partner protein that supports appetite-regulating protein
A crucial protein that helps the body manage energy and control hunger relies on a partnering molecule, new research reveals, potentially deepening our understanding of genetic obesity. In the study published today in Science Signalling, an international team led by the University of Birmingham explored the supporting role of MRAP2 alongside the appetite-regulating receptor MC3R, which orchestrates whether the body stores or burns energy.
Past work has shown MRAP2’s important role in aiding a similar receptor, MC4R, which governs hunger. This latest work asks whether MRAP2 provides the same assistance to MC3R, a structurally related protein. Using cell-based experiments, the researchers discovered that when MRAP2 is present in a 1:1 ratio with MC3R, cellular signalling improves. This suggests MRAP2 helps MC3R fulfill its job of balancing energy intake with energy expenditure. The team also pinpointed key regions of MRAP2 needed to boost signalling for both MC3R and MC4R.
Additional analyses tested whether the enhanced signalling observed with MRAP2 also occurred when MRAP2 carried obesity-linked genetic mutations. The results showed that mutated MRAP2 failed to enhance MC3R signalling, implying that MRAP2 mutations may impair the hormone system that regulates energy balance.
Dr. Caroline Gorvin, Associate Professor at the University of Birmingham and lead author, commented: “These findings offer important insights into how the hormonal system governs functions like energy balance, appetite, and puberty timing.”
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The study suggests that recognizing MRAP2 as a key helper to MC3R and MC4R opens new avenues for understanding genetic obesity risk. Insights into how MRAP2 facilitates signalling could guide the development of drugs that target MRAP2 to enhance MC3R and MC4R activity, potentially increasing fullness signals, reducing overeating, and improving energy balance in cases where diet alone isn’t enough.
The Birmingham team collaborated with the Centre of Membrane Proteins and Receptors (COMPARE), a joint initiative between the Universities of Birmingham and Nottingham. COMPARE investigates how cells communicate in health and disease to create new therapies for common conditions such as cardiovascular disease, diabetes, and cancer. The centre benefits from advanced facilities, including the COMPARE Advanced Imaging Facility, which serves researchers from academia and industry alike.
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