Fight Fat With More Fat

(By: Wired.com)

* By Hadley Leggett Email Author
* July 29, 2009 |
* 1:02 pm |
* Categories: Biology, Health, Medicine


The latest candidate for an obesity-fighting wonder drug is not what you’d expect: It’s fat.

Adding fat sounds like a strange way to curb obesity, but scientists think boosting “brown fat” — a special kind of fat that burns calories to keep people warm — might bump up metabolism and help take off pounds. Now, researchers have figured out how to turn skin cells into brown fat that sucks up energy when transplanted into mice. They’re hoping a similar strategy could someday work in people.

“Brown fat is one of the body’s natural defenses against obesity,” said cell biologist Bruce Spiegelman of Harvard Medical School, who co-authored the paper published Wednesday in Nature. “We’re trying to tap into a natural pathway involved in this kind of biology.”

Previously, scientists thought only small mammals and newborn babies harbored brown fat. But in April, three different research teams reported the presence of metabolically active brown fat in adults, located on the front of the neck and around the spine.

“It looks like it’s present in different amounts in various people,” said endocrinologist Francesco Celi of the National Institutes of Health, who was not involved in the research. Heavier people appear to have less brown fat, while slim folks have more. Scientists have speculated that increasing stores of the energy-burning fat might help maintain a proper weight, but until now, making brown fat was a mystery.

Now, Spiegelman and colleagues have identified two proteins that act as molecular “switches” to turn on the production of brown fat. In the lab, the scientists forced young skin cells from both mice and humans to make these proteins, which then transformed the skin cells into what looks and acts like natural brown fat.

kajimura-ebat-11The fat is brown because it contains extra blood vessels and mitochondria, the energy factories of the cell. But unlike most cells, which take up glucose and turn it into chemical energy, brown fat sucks up glucose and generates heat instead.

“The purpose of brown fat is to be able to burn energy upon request,” Celi said. “The classical experiment is placing a rodent in a cold room at 4 degrees Celsius. The animal is able to maintain its core temperature by burning energy, and the amount of energy that’s consumed goes up in a very substantial manner through the increased metabolism of brown adipose tissue.”

Like natural brown fat, the engineered cells burned calories at an astonishing rate. When transplanted into mice, the artificial fat consumed even more energy than expected.

“The engineered brown fat cells have same thermogenic program, but it’s not regulated by hormones the way the natural brown fat cells are,” Spiegelman said. Instead of needing to be activated by a specific chemical messenger, the engineered fat cells are always active. “They’re basically in the on position all the time.”

Being stuck in the on position might not be a bad thing, Spiegelman said. It could mean that less of the engineered fat would be needed to boost metabolism and help people lose weight. “Now that we all know that brown fat can be engineered, and that adult humans have brown fat, the question is how much does it take to alter the metabolism of a human?” he said.

The researchers see two ways their findings could translate into treatment for obesity: Either a person’s own cells could be used to make a brown fat implant, or a drug could be developed that turns on the production of brown fat inside the body.

“If we could find chemical that turns this pathway on, that would be ideal,” Spiegelman said.

Don’t expect a brown fat treatment anytime soon, though. Humans evolved to conserve energy, not waste it, and so far our clever bodies have managed to foil nearly all of scientists’ attempts to treat obesity. Even if researchers can find a safe way to make extra brown fat, Celi said, the body might compensate for lost energy by eating more or slowing down other aspects of metabolism.

“It’s a very sound and solid study,” he said. “In the long run, this could be a strategy. But from this data to the clinic, there is a long, long time.”