Metabolic switch delivers healthy fat
Mouse study spots protein that generates fuel-burning tissue.
Researchers have identified a cellular switch that triggers the production of 'good' fat cells, which pump out heat and raise the body's metabolic rate. The discovery, made in mice, might one day provide a way to treat or prevent obesity in humans.
In adult humans, nearly all fat tissue is made of white fat cells, which store excess energy for later use. But brown fat cells have a high metabolic rate and burn up the chemical fuel, rather than store it. A higher proportion of babies' fat is brown, probably as a way to keep warm. But these deposits are mostly lost after infancy.
Researchers led by Bruce Spiegelman at the Dana-Farber Cancer Institute in Boston, Massachusetts, have now identified the protein that induces developing fat cells to become brown, not white. The next step, he says, is to find drugs that can manipulate this process in adults.
Spiegelman's team found that brown fat cells in mice contain large amounts of a protein called PRDM16, which is rare in white fat cells and other cells such as muscle and liver.
When the researchers genetically engineered developing mouse fat cells to express PRDM16, the cells became brown fat cells rather than white. And when the gene for the protein was removed from brown fat cells, the cells stopped being metabolic powerhouses. Their results appear in Cell Metabolism1.
But what induces cells to make PRDM16 remains unclear. "The question is: which hormones influence this?" Spiegelman says.
Studies of adult dogs have shown that the right cocktail of hormones can resurrect brown fat. "There's no question that it can be recalled in big animals," Spiegelman says. But this involves long-term doses of drugs such as adrenaline, which have side effects such as raised blood pressure and heart rate, and would therefore be dangerous for humans.
The search is on for more specific drugs that could help the body make more brown fat, says Spiegelman. Alternatively, immature cells in white fat deposits could be genetically engineered to turn brown, he suggests.
"It sounds a little far-fetched, but remember that in cosmetic surgery fat is removed or put in all the time," he says. "You could do liposuction, [genetically] engineer the cells and then put some of them back."
- Seale, P. et al. Cell Metab. 6, 38-54 (2007).