Discovery of Cold-Activated Brown Fat May Lead to New Obesity Treatments


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By Anne Harding
WEDNESDAY, April 8, 2009 ( — What if you had a special kind of fat in your body that burned calories instead of storing them—and it could be activated simply by spending time in the cold? According to three preliminary studies published Wednesday in the New England Journal of Medicine, you probably do.

Brown adipose tissue (called brown fat) helps babies, young children, and other small mammals stay warm by burning calories when activated by low temperatures. Scientists have been skeptical that adults retain significant amounts of brown fat on their bodies. But the new research shows that many of us—perhaps even most—do.

“The incredible excitement about this is that we have an entirely new way to try to go after obesity,” says Aaron Cypess, MD, of the Joslin Diabetes Center in Boston, lead author of one of the new studies. Every obesity drug now on the market aims at getting people to take in fewer calories, Dr. Cypess points out. The current findings, while very preliminary, suggest that drugs could be developed that fire up brown fat activity and help people burn calories faster.

The new research is important because it confirms that adults have brown fat involved in temperature regulation, while also probably playing a role in whether a person is lean or overweight, says Jan Nedergaard, PhD, a professor at the Wenner-Gren Institute at the University of Stockholm in Sweden who has been studying brown fat for 30 years but was not involved in the current research.

“Brown fat can be a very significant player in the game of how we react to the food we eat and whether we store it or burn it away,” Dr. Nedergaard says.

While scientists have known about brown fat and what it does for decades, it’s been nearly impossible to study it in live humans until very recently. Finding it in people’s bodies meant taking tissue samples, so scientists mostly stuck to studying it in lab animals.

This changed when nuclear medicine specialists observed that some people had deposits of tissue that looked like fat but didn’t act like it; this fat-like tissue was located above the collarbones and in the upper chest and consumed lots of energy. Conversely, white adipose tissue—the regular fat that stores extra calories and makes us gain weight—shows very little metabolic activity.

Scientists began investigating whether this mystery tissue might be the elusive brown fat. In the new NEJM reports, three independent research teams have confirmed that this is the case, indeed, and that integrated positron-emission tomography and computed tomography (PET-CT) scans can be used not only to identify it but to measure its metabolic activity.

Next page: Who has the most brown fat?

In their report, Dr. Cypess and his colleagues reviewed 3,640 PET-CT scans performed on 1,972 patients at Beth Israel Deaconess Medical Center in Boston for various diagnostic reasons. Among women, 7.5% had patches of brown fat that were more than 4 millimeters in diameter, while 3.1% of men had similar patches.

“The people who had brown fat were, in fact, different from the people who didn’t,” Dr. Cypess explains: They were younger and leaner. People who were older, those who were obese, and those using heart drugs called beta blockers were less likely to have brown fat.

Dr. Cypess and his team also found that people whose scans were done in the winter had the most brown fat, while those scanned in the summer had the least; people who underwent the tests in the spring or fall fell in the middle.

Researchers from the Maastricht University Medical Center in the Netherlands, in the second study, looked at how temperature affected brown fat activity in 24 healthy men, also using PET-CT. When the volunteers sat in a room kept at 72° F for two hours, none of their scans showed brown fat activity. But when they were exposed to slightly chillier conditions—about 61° F—23 showed brown fat activity. The 10 men who were lean (with body mass indexes of less than 25) had more brown fat than the 14 who were overweight or obese, and their brown fat was also more active.

“That’s really new, that so many people do have brown adipose tissue,” says lead author Wouter D. van Marken Lichtenbelt, PhD.

In the third study, Sven Enerback, MD, of the University of Goteborg in Sweden, used PET to examine how cold temperatures affected brown fat activity, this time in five people. Participants spent two hours in a room kept at 63° F to 66° F. During the scan, they submerged one foot in ice water, alternating five minutes in the water and five minutes out. The cold conditions boosted the amount of glucose the study participants’ brown fat consumed by a factor of 15.

In an accompanying editorial, Francesco Celi, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., notes that “taken together, these studies point to a potential ‘natural’ intervention to stimulate energy expenditure: Turn down the heat and burn calories (and reduce the carbon footprint in the process).”

This is obviously an oversimplification, Dr. Celi says, but the demonstration that adults have brown fat that can be activated is, nevertheless, “powerful proof of concept” that the tissue could be a target for obesity-fighting drugs or even environmental fat-fighting strategies.

While Dr. Cypess is excited about the possibility of drugs that help people burn more calories, he warns that such medicines wouldn’t allow people to slim down without eating healthy and becoming more active.

The maximum amount of extra energy that people with relatively large brown fat deposits can burn probably tops out at about 500 calories. “It doesn’t take much extra food to eliminate any benefit you’ve got,” he says. “I personally don’t think that hanging out in the cold is going to be an effective way of fighting obesity.”