The Truth About Metabolism

Have you ever wondered why you gain weight so easily, while your best friend never seems to put on a pound? Preliminary research suggests you may be able to chalk it up to genetics.

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Researchers at Boston Children’s Hospital and Harvard University have identified a specific gene in the brain called MRAP2 that may control how quickly the body burns calories and in which the mutations increase the likelihood that a person will become obese, according to a study published Friday in the journal Science.

“We’ve known for the past 15 years that a gene called MC4R helps speed metabolism and depress appetite,” Joseph Majzoub, chief of endocrinology at Boston Children’s Hospital and professor of pediatrics at Harvard Medical School, told Yahoo! Shine. “What we’ve discovered is that when gene Mrap2 is mutated—at least in mice—it prevents MC4R from working effectively.”

When MRAP2 is working normally, it sends signals of satiation to the brain (“Stop eating now!”), suppressing appetite so a person doesn’t gain weight. When it’s mutated, it can’t function normally and as a result, the body clings to whatever calories it consumes. Not surprisingly, this leads to overeating and weight gain, since the body never gets the memo that it should feel full.

Majzoub and his staff wanted to know exactly what would happen if MRAP2 were mutated, so they studied both mice and obese people. In the mice study, researchers divided the rodents into two groups and deleted the gene Mrap2 in one of the groups. Both groups were fed the same diet and exercised the same amount.  Yet the mice without the MRAP2 gene gained weight—twice as much as their siblings—and kept gaining as they grew older. In fact, the only way they could keep their weight down was to eat 10 to 15 percent less than their thinner counterparts. “These mice aren’t burning the fat, they’re somehow holding onto it,” Mazjoub said in a press release. “Mice with the genetic mutation gained more weight, and we found similar mutations in a cohort of obese humans.”

For the human study, Majzoub teamed up with Sadaf Farooqi, a senior research associate at the University of Cambridge, and analyzed 500 almost people who were extremely obese and 500 people of normal weight. “We discovered that less than 1% of obese people carried potentially harmful MRAP2 mutations, but we also found various other gene mutations in both obese and nonobese subjects,” said Majzoub. While the potentially harmful gene mutations are rare, the other gene mutations may have an impact on metabolism and trigger obesity especially when combined with other mutations and environment.

The findings are exciting because obesity has often been blamed on lack of motivation. “If the cause is actually a matter of metabolism, in a far future, we may be able to design drugs that act on the MRAP2 pathway to more effectively control metabolism and weight,” he says.

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