A protein essential to the human body for managing energy and regulating appetite relies on a partner protein, according to new research, and the findings could help researchers better understand genetic obesity.
In a paper published in Science Signalling today (Tuesday 16 December), an international research team led by academics from the University of Birmingham, looked at the supporting role of a partner protein called MRAP2 with an appetite regulating protein called MC3R, which coordinates whether the body stores energy or burns it.
Previous studies have shown that MRAP2 plays a key supporting role for a similar protein (MC4R), which controls hunger, and this latest study attempted to discover whether MRAP2 worked in the same way for the structurally similar protein MC4R.
Using cell models, the team found that the presence of the MRAP2 protein, in a 1:1 ratio with MC3R, improved cellular signalling. The findings suggest that this supporting protein may help MC3R perform its role in balancing energy intake and energy use. The team also identified critical parts of MRAP2 that are needed to accomplish its role in aiding both MC3R and MC4R signalling.
Further analysis looked at whether the same enhanced signalling action was seen with MRAP2 with genetic mutations seen in some people with obesity. The team found that when mutated supporter proteins (MRAP2) were introduced to MC3R, there was no enhanced signalling of the appetite regulating protein. The findings suggest that mutations in the MRAP2 protein contribute to reducing the normal functioning of the hormone system that regulates energy balance.
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."
Understanding the tools that MRAP2 uses to aid signalling will help researchers determine whether drugs targeting MRAP2 could boost its ability to help modulate MC3R and MC4R. These drugs could enhance feelings of fullness, reduce overeating and improve the body's energy balance to help with weight loss that isn't manageable with dieting alone.
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 unique cross-University Research Centre between the Universities of Birmingham and Nottingham aimed at investigating the mechanisms of cell communication in physiology and disease to develop innovative therapies for common conditions such as cardiovascular disease, diabetes or cancer. COMPARE is supported by dedicated, state-of-the-art facilities, including the COMPARE Advanced Imaging Facility, which is open to internal and external researchers from both academia and industry.
