Scientists Identify Tiny Protein That Regulates Human Hunger and Appetite - Video

Our bodies are wired with a delicate communication network that tells us when to eat, when to stop, and how to use energy. But new research reveals this system doesn’t work alone. Scientists at the University of Birmingham and their international collaborators have discovered that the protein responsible for controlling appetite and metabolism depends on a “helper” molecule to function properly. Published in Science Signaling, the study deepens our understanding of how genetic factors influence obesity risk and could pave the way for new treatments that strengthen the body’s natural appetite control.

At the center of the discovery is MRAP2, a small but powerful protein that works alongside the appetite-regulating receptor MC3R. Together, these two proteins help decide whether the body stores or burns energy. While previous studies had linked MRAP2 to another hunger-related receptor, MC4R, this study explored whether the same supportive relationship existed between MRAP2 and MC3R—two close molecular relatives that play complementary roles in keeping metabolism balanced.

Using cell-based models and advanced signaling assays, researchers watched how the two proteins interacted. When MRAP2 and MC3R were present in equal amounts, cellular signaling activity surged, showing that MRAP2 amplifies the strength of MC3R’s communication. Without MRAP2, that signal weakened, suggesting the appetite control system starts to “lose its voice.” Further analysis revealed which regions of MRAP2 are critical for supporting these signals through both MC3R and MC4R pathways.

The team then examined genetic mutations in MRAP2 found in some people with severe obesity. These altered forms of the helper protein failed to boost MC3R activity, disrupting normal energy balance. Essentially, MRAP2’s “supportive handshake” was broken—leaving the body less able to fine-tune hunger cues and fat storage.

By revealing how MRAP2 guides this hormonal network, scientists now see new possibilities for targeted therapies that enhance fullness signals and correct appetite dysregulation—offering hope for people struggling with weight control where diet and exercise alone fall short.

REFERENCE: Aqfan Jamaluddin, Rachael A. Wyatt, Joon Lee, Georgina K. C. Dowsett, John A. Tadross, Johannes Broichhagen, Giles S. H. Yeo, Joshua Levitz, Caroline M. Gorvin. The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling. Science Signaling, 2025; 18 (917) DOI: 10.1126/scisignal.adu4315