New gene associated with obesity

According to WHO obesity and overweight are defined as abnormal or excessive fat accumulation that presents a risk to an individuals health. In 2005 approximately 1.6 billion adults over the of age 15+ were overweight, at least 400 million adults were obese and at least 20 million children under the age of 5 years were overweight.

In year 2007 researchers identified the first ‘obesity gene’, known as the FTO gene (Fat mass and obesity-associated protein). In may 2013, researchers has identified seven new sites on the human genome where tiny differences in the genomic structure affect the risk of obesity. Now in July 2013  researchers at Boston Children's Hospital have identified a genetic cause of severe obesity.

They conduct their research on mice. The affected gene, Mrap2 in mice, has a human counterpart (MRAP2) and appears to be involved in regulating metabolism and food consumption. They found that mice with the genetic mutation gained weight even while eating the same amount of food as their normal counterparts. Mice with gene mutation aren't burning the fat.

The protein created by the Mrap2 gene appears to facilitate signaling to a receptor in the brain called Mc4r, which helps increase metabolism and decrease appetite as part of a larger signaling chain involved in energy regulation. Fat cells produce the hormone leptin, prompting receptors in the brain to instigate production of a second hormone, αMSH. Mc4r detects this hormone with the aid of Mrap2, leading to a decrease in appetite and weight. Mutations in this signaling chain, including mutations in Mc4r, are known to increase the likelihood of obesity. 

They studied on a mice with the Mrap2 gene knocked out both overall and just in the brain. In both cases, the mice grew to about twice their normal size.Weight gain was greatest when both copies of Mrap2 were knocked out, but the mice still showed weight gain and appetite increase with one working copy of the gene. The weight gain was more pronounced in males than females.

The mice without Mrap2 didn't eat more at first, they still gained weight faster than the controls. Later, their appetites increased and they continued to gain more weight than the controls, even when held to the same diet and quantity of food. In the end, the mice carrying the new mutation must be fed about 15 percent less than normal mice to have the same amount of weight gain.

To investigate the gene in humans,researchers investigate groups of obese patients from around the world. Of 500 people with severe obesity, the researchers found only four people with the gene mutations.

While the finding suggests that these rare mutations directly cause obesity in less than 1 percent of the obese population, the researchers suspect that other mutations in the gene might occur more commonly and might interact with other mutations and environmental factors to cause more common forms of obesity.

The research was published in journal science.