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Scientists Identify "master Switch" for Brown Fat in Mice

Scientists have identified a "master switch" for the production of brown fat, a type of adipose tissue that generates heat and counters obesity caused by overeating , by conducting experiments on mice.

Dr. Bruce Spiegelman of Dana-Farber Cancer Institute believes that turning up the equivalent switch in humans may be a new strategy for treating obesity.

The researchers are now planning to rev up the control in mice and overfeed them to see if they are resistant to becoming obese.

"Brown fat is present in mice and in human infants, where it keeps them warm by dissipating food energy as heat, instead of storing it as white fat," said Dr. Spiegelman, senior author of the paper published in the journal Cell Metabolism.

"Human adults don't have much brown fat, but there is some, and from a therapeutic perspective the question is whether that pathway can be reactivated," he added.

Dr. Spiegelman revealed that the pathway is controlled by a gene called PRDM16, found in brown but not in white fat, which stores excess calories and causes waistlines to bulge.

In some mouse experiments, the researcher inserted PRDM16 genes into precursors of white fat, and implanted the white fat precursors under the skin of the animals. The PRDM16 gene coaxed those cells to generate brown fat cells.

"These results illustrate that the gene we identified can turn on a broad program of brown fat cell development when we insert it into precursors that otherwise would produce white fat," Dr. Spiegelman said.

Upon further analysis, the researcher observed that PRDM16 triggered formation of brown fat cells in part by turning on a metabolic pathway controlled by PGC-1alpha and the gene UCP1, which allows cells to release large amounts of energy as heat.

The researchers believe that engineering cells with PRDM16 may work as obesity preventive in humans, if their continued research in mice shows promising results once again.

"You might not have to implant a large amount of engineered precursors in people who are at risk for being obese. In theory, you would only have to reduce the accumulation of white fat by 1 percent or so to have an effect," said Dr. Spiegelman.


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