Harvard Study Swaps Bad Fat for Good in Effort on Obesity

Harvard University scientists gave white fat, which stores energy, the calorie-burning properties of brown fat, which keeps hibernating bears warm in the winter, in a development that may lead to new therapies for obesity.

Brown fat was thought to exist in humans only in babies until 2009, when three research groups found it in adults. In the study released today, scientists manipulated white fat cells in mice by blocking an enzyme used to control the cells’ creation and activity. The process gave them the energy-expending characteristics of brown fat cells.

The findings in the journal Nature Medicine were the most dramatic in visceral fat in the belly that contributes to heart disease and diabetes, said Jorge Plutzky, a senior study author and director of the Vascular Disease Prevention Program at Brigham and Women’s Hospital and Harvard Medical School in Boston. Natural variations in the level of the enzyme may help explain why some people are naturally leaner than others, he said.

“We have discovered a pathway that controls whether fat will be white or brown, and it can be manipulated, especially in the visceral fat,” Plutzky said in a telephone interview. “It’s proof of concept. It’s conceivable that this might be a way to target visceral fat in humans.”

Mice that were bred without the enzyme or treated with an experimental approach to squelch it had less weight gain and lower blood sugar levels than normal mice.

Obesity in U.S.

Two-thirds of U.S. adults are overweight, according to the Atlanta-based Centers for Disease Control and Prevention. No new drug has been approved in more than a decade to help reign in what public health officials call an epidemic of obesity, while more effective surgical procedures carry additional risks and are offered only to the heaviest patients.

The Harvard researchers homed in on an enzyme called Aldh1a1, which is produced when the body breaks down vitamin A. It was found at high levels in abdominal fat that surrounds the liver, kidneys and other organs. When the enzyme was blocked, mice put into cold rooms were able to maintain their body temperature, a defining characteristic of heat-generating brown fat and another sign of the cell transformation.

“We have conferred upon the mice protection against cold,” Plutzky said. “If you manipulate this target, you can make white fat more brown-like.”

This isn’t the first time scientists have changed the characteristics of white fat. A January study found that a hormone called irisin, which is released during exercise, makes mice lose weight and improved their blood sugar levels. That compound has been licensed by Ember Therapeutics Inc., a closely held Boston-based company. Brown fat can also be stimulated with cold exposure and exercise.

The National Institutes of Health, the Mary K. Iacocca Professorship and the Austrian Science Fund funded the Harvard study.

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