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‘Brown fat’ may be key in obesity battle

Calories burned instead of stored

By Carolyn Y. Johnson
Globe Staff / August 11, 2009

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It’s fat as you’ve never thought of it before: A few ounces can burn off up to a fifth of a day’s calories.

Recent discoveries are highlighting a good type of fat, called “brown fat,’’ that offers a potential new weapon to scientists looking for ways to fight obesity.

Unlike better-known white fat, brown fat converts stored energy into heat.

It was long known to exist in infants but had been thought to disappear with age. Then this spring, three research groups reported that brown fat exists in at least some adults. And two groups of Boston researchers have reported finding cellular switches that can be flipped on to make brown fat cells out of ordinary skin cells and other types of cells.

“This is definitely a very big change in our thinking, because it really does mean now there is an opportunity to really work with this as a way to burn off energy,’’ said Dr. C. Ronald Kahn, head of obesity and hormone action research at the Joslin Diabetes Center who is involved in both lines of research.

The discoveries raise the possibility that in the future, obesity could be treated by spurring the growth of brown fat cells in patients, transplanting such cells, or increasing the activity level of patients’ existing brown fat, Kahn said.

Obesity occurs when the balance between what we eat and the energy we burn is out of whack, causing excess calories to be stored in white fat. Many obesity interventions have focused on limiting how much food is taken in by the body whether through diet, stomach surgery, or drugs that limit appetite or food absorption.

Exercise also offers an effective way to burn more calories, but as Dr. Francesco S. Celi, a clinical investigator at the National Institute of Diabetes and Digestive and Kidney Diseases, says, “It’s proven, but it’s tough.’’ The new research, he said, allows scientists to start thinking seriously about new ways of upping the calorie burning side of the equation.

The interest in brown fat is driven by two separate lines of work that converged this year: one built on years of painstaking work to elucidate how such cells formed in the body, and another that was almost serendipitous, employing a type of scan usually used to identify cancer.

“These two lines of research together have made this very exciting,’’ said Bruce Spiegelman, a professor of cell biology at the Dana-Farber Cancer Institute who has done leading work on brown fat. “Like many areas of science, once a door is cracked open, lots of investigators look to walk through.’’

Spiegelman has spent years investigating brown fat formation, finding last summer that it is possible to turn immature muscle cells into brown fat. He reported in the journal Nature last month that his group found two proteins that turn skin cells into brown fat - which gets its color from iron-containing cellular structures that act as furnaces.

His research group took skin cells from mice, inserted genes that flipped the molecular switches to force the cells to turn into brown fat, then transplanted the tissue into mice. Imaging showed that the tissue was active, like normal brown fat.

The experimenters also successfully changed human infants’ foreskin into brown fat in a lab dish. Spiegelman said future research will examine whether increasing brown fat affects a mouse’s weight, and whether it might be possible to do something analogous in people.

Kahn and colleagues have also been studying brown fat at the molecular level and last year described a protein that spurred cells to become brown fat in mice. They found that when they increased the levels of the protein, it boosted how much energy the mice burned, and reduced weight gain, compared with a group that did not receive the treatment.

All the work, outside scientists said, is likely to spur pharmaceutical companies to look at ways to trigger brown fat - whether it is a drug that can promote brown fat growth or activity, or taking cells, turning them into brown fat in a dish, and transplanting it back into people.

These still-early findings took on far greater significance because of the research showing that brown fat naturally exists in adults.

Brown fat is found on babies’ backs between their shoulder blades and helps keep them warm by generating heat. It was long thought to disappear with age, but radiologists, who look for tumors using a specific type of imaging that measures glucose uptake, consistently saw areas in patients that weren’t tumors but were surprisingly active. Some scientists wondered if the hot spots could be brown fat.

Kahn and colleagues reviewed scans from nearly 2,000 patients and found deposits of brown fat in the chest regions of some of them, confirmed by tissue analysis. Brown fat was more likely to be seen in younger patients, and those who were less obese. Two separate groups of scientists reported similar results at the same time, including a group of European researchers who - by scanning five people placed in a cold room and whose feet were intermittently placed in ice water - found that cool temperatures spur brown fat activity.

Still, researchers cautioned that brown fat discoveries are far from a treatment for obesity and will need to be investigated more carefully.

Pharmaceutical companies have tried to develop drugs to amp up calorie burning, according to Dr. John Amatruda, senior vice president of diabetes and obesity at Merck. But “there are downsides to it,’’ said Amatruda. “When you increase metabolic rate, you increase heat production, you increase heart rate, you perspire, your temperature may go up.’’

The physiological effects of increasing brown fat will need to be carefully examined, but Dr. Mitchell Lazar, director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania School of Medicine, said that because brown fat’s normal job in the body is to burn energy, it is an exciting new avenue for research.

“There is hope in terms of a new direction,’’ Lazar said. “But . . . it’s still early-stage.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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