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Scientists Find How Obesity Gene Works, A Clue To Treatment

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MIAMI (CBSMiami/AP) – Scientists have finally figured out how the key gene tied to obesity makes people fat, a major discovery that could open the door to an entirely new approach to the problem beyond diet and exercise.

The work solves a big mystery: Since 2007, researchers have known that a gene called FTO was related to obesity, but they didn't know how, and could not tie it to appetite or other known factors.

Now experiments reveal that a faulty version of the gene causes energy from food to be stored as fat rather than burned. Genetic tinkering in mice and on human cells in the lab suggests this can be reversed, giving hope that a drug or other treatment might be developed to do the same in people.

The work was led by scientists at MIT and Harvard University and published online Wednesday by the New England Journal of Medicine.

The discovery challenges the notion that "when people get obese it was basically their own choice because they choose to eat too much or not exercise," said study leader Melina Claussnitzer, a genetics specialist at Harvard-affiliated Beth Israel Deaconess Medical Center. "For the first time, genetics has revealed a mechanism in obesity that was not really suspected before" and gives a third explanation or factor that's involved.

"Being obese or overweight is not always because you are lazy or not eating properly or being physically active. It can be because you're genetically pre-disposed," said Dr. Gianluca Iacobellis, an endocrinologist at UHealth – University of Miami Health System.

"You may be pre-disposed to become more obese because some mild defect in the activity of these genes which are no longer able to switch from the white fat to the brown fat," Dr. Iacobellis said.

It's long been known that brown or beige fatty tissue -- the so-called "good fat" -- burns calories, while the more common white fat stores them. The body constantly makes fat cells, and the two genes determine whether they become brown or white ones.

The FTO gene turns out to influence obesity indirectly, as a master switch that affects two other genes that control thermogenesis, or burning off energy.

In one experiment described in the medical journal, researchers blocked the faulty gene's effect in mice and found they became 50 percent leaner than other mice despite eating a high-fat diet, and burned more energy even when asleep.

In other tests on human cells, blocking the gene's effect increased energy burning in fat cells. Editing out the problem gene in human cells in the lab also restored normal metabolic function.

Several obesity drugs are already on the market, but they are generally used for short-term weight loss and are aimed at the brain and appetite; they don't directly target metabolism.

Researchers can't guess how long it might take before a drug based on the new findings becomes available. But it's unlikely it would be a magic pill that would enable people to eat anything they want without packing on the pounds. And targeting this fat pathway could affect other things, so a treatment would need rigorous testing to prove safe and effective.

"If we can manipulate the fat cell, we can open up new avenues of treatment for obesity and obesity related disease," Dr. Iacobellis explained.

Obesity affects more than 500 million people worldwide and contributes to a host of diseases. In the U.S., about one-third of adults are obese and another one-third are more modestly overweight.

(TM and © Copyright 2015 CBS Radio Inc. and its relevant subsidiaries. CBS RADIO and EYE Logo TM and Copyright 2015 CBS Broadcasting Inc. Used under license. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed. The Associated Press contributed to this report.)

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