In a study conducted on mice, researchers found a particular gene responsible for severe obesity, irrespective of the amount of food they consumed.
Researchers at Boston Children's Hospital found that improper diet and lack of exercise are not the only two factors responsible for obesity. In a study conducted on mice, a team of researchers identified a genetic cause of severe obesity, though this condition is rare.
Mrap2 is a gene present in the body that creates a protein that sends signals to a receptor in the brain called Mc4r to increase metabolism and decrease appetite. The hormone leptin, which is produced by fat cells, sends a signal to the brain to instigate the production of another hormone known as αMSH. The brain receptor Mc4r is able to identify this new hormone with the help of Mrap2 and once it receives confirmation that the production of αMSH has begun, it increases metabolism and decreases appetite. Any alteration made to the Mrap2 gene can hamper this signal process.
For the study, researcher observed mice that had alterations made to either Mrap2 in the brain and overall Mrap2s. Researchers found that in both cases mice grew to twice their size. Though weight gain was much more in mice that had their overall Mrap2s altered, some mice that had only one copy of Mrap2 altered also showed significant weight gain. Researchers also observed that weight gain was more prominent in males than females. Additionally, mice that had no Mrap2 at all, significantly gained weight when fed a high-fat diet than normal mice. Though these mice didn't eat too much food at first, they gained weight faster than normal mice.
"These mice aren't burning the fat, they're somehow holding onto it," the study's lead investigator, Joseph Majzoub, MD, chief of endocrinology at Boston Children's, said in a press release. "Mice with the genetic mutation gained more weight, and we found similar mutations in a cohort of obese humans."
Researchers then went on to analyse whether the same gene mutation can be held responsible for obesity in humans. They conducted a further study on 500 participants that had severe, early-onset obesity and found four changes in the human equivalent of Mrap2.
While researchers confirm that these mutations are rarely the cause of obesity, affecting one percent of the population, they wonder whether other mutations in the gene might occur more commonly and cause other forms of obesity by interacting with environmental factors.
"We found other mutations that weren't as clearly damaging to the gene," notes Majzoub. "It's possible that some of these more common mutations actually are pathogenic, especially in combination with other genes in the same pathway."
Majzoub hopes to conduct further studies on the same topic by studying more obese populations, tracking their diet and physical activity levels as well as understanding whether this gene mutation also alters energy balance.
Findings of the research were published in the journal Science on July 19.
