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Studies Find A Way Adult Bodies May Fight Obesity

By David Brown
Washington Post Staff Writer
Thursday, April 9, 2009

Three new studies show that most adults have unexpectedly large and active deposits of a calorie-burning type of fat that biologists once thought disappeared after infancy.

The persistence of brown fat suggests a potential new strategy to fight obesity, which is epidemic in the United States and increasing rapidly in the developing world. In addition to eating less and exercising more, people may one day be able to stimulate their bodies to get rid of stored energy -- in the form of ordinary fat -- purely as heat.

"It is, in a sense, the discovery of a new organ," said Sven Enerback, a researcher at the University of Goteborg in Sweden and the lead author of one of three studies appearing today in the New England Journal of Medicine.

"This is a tissue whose sole physiological purpose is to expend energy," said Francesco S. Celi, a metabolism researcher at the National Institutes of Health, whose commentary accompanies the studies. "That makes it an ideal target" for drugs or other measures designed to make it more active.

At the moment, however, the only safe way to activate brown fat is to stay chilly, right at the verge of shivering, for prolonged periods. That reproduces the conditions that led to the evolution of brown fat -- namely, life-threatening cold in babies and small furry animals that cannot put on clothes to keep themselves warm.

Although the new research poses a difficult question -- Which would you rather be, thin or warm? -- the ultimate goal is to find a less uncomfortable way exploit this ancient adaptation.

The three studies add to the emerging view that brown fat is involved in the body's complicated energy balance and may play a role in diseases such as Type 2 diabetes that can arise when that balance is thrown off.

For example, leaner people have more detectable brown fat than overweight people. Brown fat also appears to be more active in women than men, even though obesity is more prevalent in women. Studies show that stimulating the production of brown fat in mice -- a species in which it is naturally plentiful -- makes them resistant to gaining weight or to developing diabetes when fed a high-calorie diet.

In humans, it is unclear whether brown fat is more a cause of leanness or a result of it.

Virtually all cells have microscopic "power plants" called mitochondria, where energy sources such as sugars and fats are burned to produce a compound called ATP, the universal "coin" of the body's economy. Brown fat cells are loaded with mitochondria, but in them the various enzymes that lead to the production of ATP are "uncoupled" from one another. The result is that the energy in the glucose and fat is lost as heat, the way the work of a car engine is lost as heat if the car is stuck in a snowbank with its tires spinning.

In one of the new studies, researchers at Maastricht University Medical Center, in the Netherlands, examined 24 young men, about half of them lean and half overweight. Each was kept in a cool room (61 degrees Fahrenheit) for two hours and then given a PET scan, which lights up any tissue that is using a lot of glucose, showing that it is highly active on a metabolic level.

After the men had been kept cold, activated brown fat deposits were seen in 23 of 24 of them. (The one in which there was no activation was the heaviest.) Lean men had about four times as much brown fat activity as the overweight men. When several were retested without first being cold, there was no brown fat activity.

In a second study, the Swedish team led by Enerback kept five volunteers in a cool room for two hours and then gave them PET scans while intermittently putting one foot of each subject in an ice-water bath. Brown fat deposits lighted up each time. In three, the tissue was then biopsied and proved to be brown fat.

In the third study, C. Ronald Kahn and Aaron M. Cypess of the Joslin Diabetes Center in Boston examined PET scans performed on 1,972 patients for various reasons over a three-year period. What appeared to be active brown fat was visible in 7.5 percent of the women and 3.1 percent of the men.

That was a much lower prevalence of detectable brown fat found in either of the other two studies. There are a number of possible reasons.

The Boston researchers did not attempt to induce activity in the brown fat by cold exposure (although PET scans done on days when it was cold outside were more likely to light up). The study also included many elderly, overweight and diabetic patients -- all conditions in which brown fat activity is less likely.

Other studies and extrapolation from animal experiments suggest that brown fat could be responsible for as much as one-fifth of the energy we burn at rest. Fully stimulated, the tissue might be able to burn off 10 pounds in a year.

Research published last summer by Kahn and his colleague at the Joslin Center, Yu-Hua Tseng, showed that when mice are injected with a growth factor called BMP7, they develop more brown fat. Kahn said he thinks ways will be found to increase brown fat in humans "a lot, at least in activity if not in amount."

Enerback, the Swedish scientist, agreed that the search for a drug that stimulates brown fat "is definitely something we should pursue." He added, however, that "I don't think there will ever be a pill that substitutes for a fundamental change in lifestyle in the treatment of obesity."

The latest findings highlight once again the extent to which obesity is a consequence of Homo sapiens carrying into an era of abundance, leisure and warmth the physiology that evolved in a world marked by barely enough food, constant physical activity and dangerous cold.

"We are living in a very comfortable time," said Wouter D. van Marken Lichtenbelt, a physiologist at Maastricht University who led the Dutch study. "But we did not evolve in such a time."

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