For more than 30 years, scientists have been intrigued by brown fat, a cell that acts like a furnace, consuming calories and generating heat. Rodents, unable to shiver effectively to keep warm, use brown fat instead. So do human infants, who do not shiver very well. But it was generally believed that humans lose brown fat after infancy, no longer needing it once the shivering response kicks in.
That belief, three groups of researchers report, is wrong.
Their papers, appearing Thursday in The New England Journal of Medicine, indicate that nearly every adult has little blobs of brown fat that can burn huge numbers of calories when activated by the cold, as when sitting in a chilly room that is between 61 and 66 degrees.
Thinner people appeared to have more brown fat than heavier people; younger people more than older people; people with lower glucose levels, presumably reflecting higher metabolic rates, had more than those whose metabolisms were more sluggish; and women had more than men. People taking beta blockers for high blood pressure or other medical indications had less active brown fat.
“The thing about brown fat is that it takes a very small amount to burn a lot of energy,” said Dr. C. Ronald Kahn, head of the section on obesity and hormone action at the Joslin Diabetes Center in Boston.
The fat really is brown, researchers say, because it is filled with mitochondria, the tiny energy factories of cells. Mitochondria contain iron, giving the tissue a reddish brown color.
The hope is that scientists may find safe ways to turn on peoples’ brown fat, allowing them to lose weight by burning more calories. But researchers caution that while mice lose weight if they activate brown fat, it is not clear that people would shed pounds — they might unwittingly eat more, for example. The data on global patterns of obesity are not good enough to say whether living in a cold climate makes people thinner.
The best evidence for the effects of brown fat is from earlier studies in mice, said Leslie P. Kozak, a professor of molecular genetics at the Pennington Biomedical Research Center of Louisiana State University.
Recently, Dr. Kozak put mice predisposed to obesity in a cold room, 41 degrees, for a week. The animals activated their brown fat. As a result, they lost 14 percent of their weight, which constituted 47 percent of their body fat, while eating a high-fat diet with two and a half times more calories than they had consumed at room temperature.
“That’s just by going out in the cold, without any drug treatment,” Dr. Kozak said. But, he cautioned, mice, small animals with a comparatively huge surface area, are easily chilled. “Put the mouse in the cold,” he added, “and it becomes a heat producing machine.”
Jan Nedergaard of the University of Stockholm did the opposite of Dr. Kozak. He and Barbara Cannon, also at the University of Stockholm, studied mice that were genetically engineered so their brown fat could not burn calories. The animals became fat.
“Until very recently, we would have said that it is doubtful that differences in brown fat really could contribute to obesity,” Dr. Nedergaard said. Now, he said he had changed his mind, at least for mice.
The key to finding brown fat in humans was PET-CT scans. The PET scans pinpoint areas where cells are actively burning glucose and the CT scans identify it as fat. Because brown fat rapidly burns glucose to produce heat, it lights up in PET scans. In two of the three studies, investigators also studied samples of brown fat that were removed from a few subjects, confirming that the cells had a protein, UCP-1, that is unique to brown fat.
Brown fat in adult humans was in an unexpected place. Infants have it mostly as a sheet of cells covering their backs. Rodents have it mostly between their shoulder blades, just down from the neck. But in adult humans, it showed up in the upper back, on the side of the neck, in the dip between the collarbone and shoulder, and along the spine.
That may be one reason it was missed for so long, Dr. Kahn said.
“There was an interest in looking at humans 20 or 25 years ago with different scanning techniques, but people were always looking between the shoulder blades,” he said. And since there is so little brown fat — just a few grams of tissue — it can be hard to find, Dr. Kahn added.
His study, one of the three published Thursday, involved 1,972 people who had had PET-CT scans for a variety of reasons. The scans showed brown fat in 7.5 percent of the women and 3 percent of the men — an underestimate, Dr. Kahn says, because the people had not activated brown fat by getting cold.
Dr. Kahn and his colleagues also examined surgical samples taken from the necks of two patients. They concluded that what looked like brown fat in their scans was indeed brown fat.
A second study, led by Wouter D. van Marken Lichtenbelt of Maastricht University in the Netherlands, involved 24 healthy young men. Ten were lean, the rest overweight or obese.
The scans showed no brown fat when the men had been in a room that was a comfortable temperature. But after they were in a chilly room for two hours, scans showed brown fat in all but one, an obese man.
A third study, led by Dr. Sven Enerbäck of the University of Goteborg in Sweden, involved five healthy adults. Each had two scans — one after being in a room at a comfortable temperature, the other after being in a chilly room for two hours. The investigators saw brown fat in their chilled subjects. Three participants allowed the researchers to remove some white fat and some brown fat to demonstrate that what looked like brown fat in the scans really was that elusive substance.
The studies, investigators say, should stimulate research on safe ways to activate brown fat. It is known to be activated not only by cold but also by catecholamines, hormones that are part of the fight or flight response. That is why beta blockers, which block catecholamines, can suppress brown fat activation.
Epinephrine, or adrenaline, and ephedra, an herbal supplement containing epinephrine, can stimulate brown fat, said Dr. Rudolph Leibel, co-director of the Naomi Berrie Diabetes Center at the Columbia University Medical Center. But the drugs have too many side effects to be used for weight loss, he said, adding that while caffeine can bolster ephedra’s effects, it is easy to eat your way out of a brown fat effect.
Brown fat, Dr. Leibel said, “fits the fantasy — I eat what I want and burn it off.” That, however, is still a fantasy, he added.
If a drug that stimulates brown fat could be developed, said Dr. Claude Bouchard of the Pennington Biomedical Research Center, it would be the first obesity drug to affect energy expenditure rather than appetite.
Then there is the notion of simply hanging out in a cold room.
“We’re thinking of opening a frosty spa,” Dr. Kozak said jokingly.
By GINA KOLATA