New York : Researchers have found the precise shape of a key player in human metabolism, which could lead the way to better treatments for obesity and other metabolic diseases. According to a study, published in the journal Science, the research team focused on a protein in the brain, the melanocortin 4 receptor (or MC4R).
This receptor helps with regulating the body’s energy balance by controlling how much energy is stored as fat. Mutations in the gene that encodes the MC4R protein are linked to severe childhood obesity and other forms.
“A lot of people think obesity is a lifestyle choice, but some people have mutations of this gene. And if they have mutations of this gene, many cannot control their eating. It’s this receptor causing this issue in the brain,” said study researcher Raymond Stevens from the University of South California in the US.
Severe obesity is often linked to other health issues. Recent data on coronavirus have shown that adults 65 and older who are severely obese are among the hardest hit by the illness, according to the US Centers for Disease Control and Prevention.
The research team was interested in the MC4R as part of a larger effort to elucidate the structures of a class of proteins called G protein-coupled receptors that control many human functions. MC4R is among them.
As they began to tackle the MC4R structure, they looked for the world’s expert in this area and turned to Roger Cone at the University of Michigan Life Sciences Institute for help on the function of this important receptor.
Researchers at the University of Michigan discovered the MC4R and have been studying its biology and pharmacology for more than 25 years.
Since then, four drugs have been developed to target melanocortin receptors in humans. The drug, bremelanotide, targets the MC4R to treat rare forms of syndromic obesity, which affects about one out of 1,500 people.
However, the drug is not potent enough to treat dietary obesity — a more common form of the disease. By determining the structure of MC4R, the scientists were able to see how it binds to and interacts with other drug molecules.
Knowing how the protein is configured will enable scientists to develop and test new therapies that can more precisely treat obesity, the researchers noted.