In a finding that could point the way to new weight-loss treatments, health experts at the Sanford-Burnham Medical Research Institute have identified a naturally occurring substance involved in turning on “brown fat” — a healthy type of fat that helps the body burn calories and shed pounds.
The discovery, published in the Journal of Clinical Investigation, involves a protein — dubbed p62 — that regulates metabolism in fat tissue. The research team found that when p62 is missing in fat tissue, the body's metabolic balance shifts — inhibiting "good" brown fat that can help the body burn calories, while favoring the "bad" white fat associated with obesity.
These findings suggest p62 might be the key to promising new therapies to target obesity.
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"Without p62 you're making lots of fat but not burning energy, and the body thinks it needs to store energy," said Jorge Moscat, a Sanford-Burnham professor who led the study with collaborators at Helmholtz Zentrum München in Germany and the University of Cincinnati. "It's a double whammy."
Brown fat — also called brown adipose tissue (BAT) — has become the focus of a growing body of new obesity research. It is one of two primary types of fat in the body, the other being the familiar “white” or “yellow” fat you pile on when you eat more calories than you burn and gain weight.
Brown fat — concentrated around the back, neck and shoulders — is believed to help maintain core body temperature by burning calories and fat reserves to generate heat. Until recently, scientists thought BAT disappeared in childhood. But five years ago, researchers found brown fat is also present in adults and is turned on by cold temperatures and exercise.
Recent studies have found when BAT is “switched on” by cold or exercise it can produce 300 times more heat than any other organ in the body. Women and lean younger people have more brown fat than men or heavier older individuals.
The new research suggests that, in many cases, obesity is caused by more than just overeating and lack of exercise — something happens that causes the body to store more fat and burn less energy.
The Sanford-Burnham study suggests p62 may hold the key to that process.
Moscat's team had previously produced mice that lack the p62 protein in their bodies and found the animals were obese and also had metabolic abnormalities.
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For the new study, Moscat and colleagues produced mice lacking p62 only in their fat tissue. These mice were obese, like the mice missing p62 in all their tissues, but further studies showed p62 is "a master regulator" in normal fat metabolism, Moscat said.
"This makes it easier to think about new strategies to control obesity," he said.
This study was funded by the National Institutes of Health.