Turning Up the Heat on Brown Fat
|C. Ronald Kahn, M.D.||Yu-Hua Tseng, Ph.D.||Aaron Cypess, M.D., Ph.D.|
Joslin researchers unveil secrets of the fat that may make you thinner—and less prone to diabetes
What does it take to burn off the extra weight that puts so many people at risk of type 2 diabetes and related diseases?
How about just turning down the thermostat—can a cool room burn off a handful of chocolate candy or a side of French fries?
That’s one question Joslin researchers are asking as they follow up on their 2009 discovery of energy-burning brown fat in adults.
Brown fat works opposite to white fat. White fat infamously stores extra calories as overflowing bellies, muffin tops, love handles and plump thighs. In neat contrast, brown fat expends energy in the form of heat. That’s very handy for maintaining body temperature in newborns, but brown fat takes up so little space that until recently most doctors believed adults had none.
Joslin’s C. Ronald Kahn, M.D., Aaron Cypess, M.D., Ph.D., and their colleagues looked for brown fat in the radiology scans of adults who had undergone the testing for other reasons. They found small collections of brown fat in the neck and around the collarbones that tended to show up in younger, leaner adults examined in cooler seasons, while these collections were not seen in older, obese individuals. Women had detectable brown fat twice as often as men.
Other papers published in the same issue of the New England Journal of Medicine and elsewhere since then have confirmed and extended these original observations.
In the desperate search for more effective tools to combat the twin epidemics of obesity and type 2 diabetes, the surprising possibilities of brown fat represent a potential metabolic bonanza. But this enticing idea requires a lot of fleshing out, a task in which the Kahn and Cypess labs are joined by the lab of Yu-Hua Tseng, Ph.D.
Feeling the burn
Obesity happens when energy intake exceeds energy expenditure. Brown fat may help balance the equation, if scientists can harness the energy-burning power for clinical application.
“Brown fat is not a cure for obesity,” cautions Dr. Cypess, “but burning off a hundred or more extra calories a day could add up.”
Additionally, studies in mice show that brown fat activity appears to reduce the metabolic complications of obesity, such as high blood sugar levels and low insulin sensitivity, even if the mice don’t lose weight. “We don’t know if that’s true in humans,” Dr. Kahn says.
What Dr. Cypess calls the Joslin “fat team” is at the center of a hub of projects across multiple labs designed to understand the epidemiology, biology and clinical utility of brown fat.
Among the open questions, exactly how much energy does brown fat burn? In preliminary experiments by Drs. Cypess and Kahn, normal-weight people who sit in a 59-degree room for two hours with summer clothing seem to chew up energy at a rate of 100 to 250 calories per day.
Many collaborations are filling in such gaps in knowledge as who has brown fat (in one group of kids, about 40 percent between ages 5 and 21), where it exists in adults (intermixed with white fat and muscle in some samples) and the best ways to stimulate it (so far, cold seems to work better than known drugs).
One challenge is finding a better way to measure brown fat in humans. Radiation-based imaging exposes people to small but cumulatively harmful risks. Magnetic resonance imaging (MRI) is expensive. In his office, Dr. Cypess demonstrates a bulky handheld infrared camera he’s testing. The manufacturer sells it to identify heat leakage from homes but in people it might reveal telltale brown fat hot spots.
One year before the blitz of studies trumpeting brown fat in adults, Dr. Tseng and her co-authors reported that BMP-7, a molecule used after spinal fracture surgery to promote bone growth, could expand brown fat when injected into mice. With the help of an orthopedic surgeon, she and Dr. Cypess are evaluating changes in brown fat in people undergoing spinal surgery followed with BMP-7 treatment.
Dr. Tseng is also looking for brown fat precursor or starter cells, with an eye toward the possibility of extracting a person’s own cells and transforming them for cell therapy. “Not all the brown fat cells in the body are the same,” she says. “Brown fat from different anatomical positions may come from different sources.”
In an unexpected direction, the team is also exploring the potential of white fat cells to increase their energy-burning potential and be more like brown fat cells. Brown fat gets its distinctive color from its uniquely dense mitochondria, the tiny cellular power plants that convert oxygen and food energy into cell energy or, in the case of brown fat, heat. “White fat needs more mitochondria, and it needs the special mitochondrial protein UCP1, found only in brown fat,” Dr. Kahn says.
Most recently, Tseng’s lab has identified “progenitor” cells in white fat tissue and skeletal muscle in mice that can be induced to become mature brown fat cells, complete with the UCP1 marker. The results were published in the Proceedings of the National Academy of Sciences in December 2010.
As their findings pile up, the team is rethinking all fat. “I collect fat,” Dr. Cypess remarks. “We’re making a fat map, an atlas of the entire human adipose tissue depot. Fat may be a bunch of mini-organs that have different behaviors depending where they are.”
In the meantime, Dr. Kahn wistfully calculates that stimulation of his brown fat might be equivalent to his 35-minute strenuous workout on an elliptical trainer. But when her friends ask Dr. Tseng for weight-loss advice, she tells them the best evidence supports diet and exercise. “Our research is really to benefit people with metabolic disorders who need to lose weight to restore their metabolism to a normal state,” she says.
In adults, brown fat is centered in the neck and around the collarbones.
Illustration: John MacNeill, based on patient imaging software designed by Ilan Tal.