A recent study has found that a protein important for managing energy and appetite in the human body depends on another protein for support. The research, published in Science Signalling by an international team led by the University of Birmingham, examined how the partner protein MRAP2 works with the appetite-regulating protein MC3R. MC3R is involved in deciding whether the body stores or burns energy.
Previous research established that MRAP2 plays a supporting role for another similar protein, MC4R, which helps control hunger. This latest study investigated if MRAP2 also assists MC3R in a similar way.
The researchers used cell models and observed that when MRAP2 was present in equal amounts with MC3R, it improved cellular signalling. This suggests that MRAP2 may help MC3R balance energy intake and use. The team also identified specific parts of MRAP2 necessary for aiding both MC3R and MC4R signalling.
Further experiments focused on genetic mutations seen in some people with obesity. When mutated versions of MRAP2 were introduced to MC3R, there was no improvement in signalling by the appetite-regulating protein. This indicates that changes in MRAP2 can interfere with normal hormone system functions related to energy balance.
Dr Caroline Gorvin, Associate Professor at the University of Birmingham and lead author of the study, stated: "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."
Researchers hope that understanding how MRAP2 aids signalling will lead to drugs targeting this protein. Such drugs could potentially increase feelings of fullness and help regulate overeating and weight gain when dieting alone is not effective.
The study involved scientists from the Department of Metabolism and Systems Science as well as COMPARE—the Centre of Membrane Proteins and Receptors—a collaborative research center between the Universities of Birmingham and Nottingham focusing on cell communication mechanisms in health and disease.
