Genetic Mutation Responsible for Severe Obesity Found

Researchers have now found the genetic mutation that increases the risk of developing obesity. The mutation, though rare, offer a unique insight into the genetic basis of obesity.

The study, by the researchers at Boston Children's Hospital, was conducted on a set of mice. Researchers found that an alteration in the gene Mrap2 led to mice developing obesity even when they were fed normal amounts of food. The human counterpart of this gene Mrap2 was found to be associated with increased risk of obesity in people. One theory about these kinds of rare mutations in humans suggests it helped human survive a severe famine.

"These mice aren't burning the fat, they're somehow holding onto it. Mice with the genetic mutation gained more weight, and we found similar mutations in a cohort of obese humans," said Joseph Majzoub, MD, chief of endocrinology at Boston Children's and lead author of the study, according to a news release.

The gene Mrap2 helps regulate appetite and weight. The protein secreted by this gene works along with a receptor in the brain called Mc4r, which increases metabolism and decreases hunger.

Fat cells in the body generate a hormone called leptin that gets the receptor in the brain to start producing another hormone called αMSH. Mc4r needs Mrap2 to detect αMSH, which leads to a decrease in appetite and weight. Mutation in this pathway can increase the odds of the person developing obesity.

In the study, mice with knocked out Mrap2 gene gained more weight than others. Also, the weight gain was high in mice that had both copies of the gene knocked out. Surprisingly, these mice ate the same amount of food at the start of the study as other normal mice with a functioning Mrap2 gene. It was only when they started putting on weight that they increased their food intake.

The scientists then looked at the effect of mutation of the human equivalent gene of Mrap2. They found at least four mutations resembling the human equivalent of Mrap2 among the 500 obese people. This rare kind of mutation affects about 1 percent of all obese people. Researchers believe that these mutations might be working along with other genetic changes and environmental factors in increasing the risk of obesity in people.

The study is published in the journal Science.

Obesity can raise risk of chronic conditions such as heart disease, diabetes, stroke, arthritis and even some cancers. According to estimates by CDC, a third of all people living in the U.S are obese. A previous report had shown that by 2030, the obesity rate in the U.S. would be 40 percent.