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Possible Key To Weight Loss? Researchers Find ‘Master Switch’ To Crank Up Fat-Burning

Researchers say new science on a “metabolic master switch"  may hold the promise of someday making a dent in the obesity epidemic. (Courtesy UConn Rudd Center for Food Policy & Obesity)

Researchers say new science on a “metabolic master switch” may hold the promise of someday making a dent in the obesity epidemic. (Courtesy UConn Rudd Center for Food Policy & Obesity)

Here’s my fantasy: I’ve overindulged — let’s say, purely theoretically, on Cape Cod fried clams, french fries and beer — and would normally face the greasy regret and resign myself to extra carrots and cardio in the days to come.

But no. Instead, I simply pop a pill that cranks up my metabolism for a few hours so that I burn the extra calories instead of storing them as fat. I don’t gain an ounce.

That’s a very distant prospect. But new science on a “metabolic master switch,” just out in the New England Journal of Medicine, brings my dream one step closer to reality — and, researchers say, may hold the promise of someday making a dent in the obesity epidemic.

Until now, weight-loss treatments have focused on altering appetite and exercise, says MIT computer science professor Manolis Kellis, senior author on the paper. Now, “what we have in our hands is a third knob, if you wish, for controlling body fat,” he says. “It’s working directly on your fat cells to reprogram them to burn more energy rather than to store it as fat.”

In normal-weight mice, Kellis says, the effects of turning that knob are dramatic: “By changing the expression of one gene in these mice, they lose 50 percent of their body weight. You can feed them all the fat you want and they will not take on weight. They do not exercise more and they do not eat less, what they do is simply burn more energy when they’re awake, or even in their sleep.”

Dr. Melina Claussnitzer is lead author on the fat-burning paper just out in the New England Journal of Medicine. (Courtesy of Lovely Valentine)

Dr. Melina Claussnitzer (Courtesy of Lovely Valentine)

But mice are not men, of course. Could this work in humans?

“We experimented on human fat cells,” says Melina Claussnitzer, first author of the paper, a visiting professor at MIT and faculty member at Beth Israel Deaconess Medical Center. “And we found that we could flip them from energy-storing to energy-burning by altering the expression of a single gene — and, even more remarkably, by altering a single letter from our 3-billion-letter genome. And we could flip that switch back in either direction.”

Still, it’s a very long way from genetically editing human cells in a Petri dish to altering the metabolism of a breathing human, the researchers caution. The team has filed patents on their switch-flipping manipulations and are seeking to commercialize the approach and lead it into human clinical trials, Kellis says, but cannot speculate on a time frame.

So meanwhile, there’s no such thing as a free fried clam. But we can at least savor the story of how this cutting-edge science came to be.

Let’s begin in 2007, when researchers turned up the first genetic link to obesity, a region of the genome called FTO. To this day, it remains the strongest genome-obesity link: Some 44 percent of Europeans, it turns out, have a version that predisposes them to weigh more, on average five to seven pounds.

The natural next question was: How does it work? Does it make people eat more? Move less? Both?

Or neither, says Claussnitzer. “Despite seven years of intense efforts to hunt down a mechanism, no link has been made between the genetic differences in the region and altered functions in the brain.” Continue reading

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