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Flipping the Slim Switch

Turning down that second slice of cheesecake and visiting the gym go a long way towards fighting those love handles, but a new study now points to a biological switch that prevents flab.

A protein called Wnt controls fat formation by reining in two factors found in the nucleus of immature fat cells, say researchers at the University of Michigan in Ann Arbor. Researchers believe that the findings, in today’s issue of the journal Science, could in the future lead to ways to control weight.

Roughly 97 million Americans are either overweight or obese, the health risks of which include heart disease, high blood pressure and diabetes.

According to senior author Ormond MacDougald, immature fat cells secrete Wnt, which binds to Wnt receptors, triggering a cascade of chemical signals within the cell that inhibit the activity of two fat-forming factors found in the nucleus. When activated, these factors, CCAAT/enhancer binding protein a (C/EBPa) and peroxisome proliferator-activated receptor g (PPARg), make pre-fat cells balloon into mature fat cells.

During normal cell growth, one critical event is when immature fat cells stop making Wnt, essentially releasing the brakes on fat formation, says MacDouglad. That lets C/EBPa and PPARg come to the fore. “Those two factors working together are sufficient to turn on all the genes that are required to make fat cells.”

Once these factors start working, the conversion takes place within about a week, says MacDougald. Along with obvious structural changes, he says, “the [fat cell] acquires the ability to respond to the metabolic hormones, like insulin.”

The researchers were also surprised to find that if Wnt is shut off, pre-muscle cells can also turn into mature fat cells.

According to M. Daniel Lane, a professor of biological chemistry at Johns Hopkins University School of Medicine in Baltimore, Md., “it seems likely that Wnt would be involved in increasing the number of fat cells in obese individuals.”

So what turns Wnt off? In short, researchers don’t know. But over the next one to two years, more studies will look into how it’s controlled, with hopes of eventually developing targets for anti-obesity therapy. “If you up-regulated Wnt production,” says Lane, “this might down-regulate conversion to fat.”

What To Do

MacDougald cautions that this research is in its earliest stages, and any clinical application is years away. As well, he says, “the Wnt signaling pathway is used by many different tissues, and so the specificity of the drugs would be complicated.”

Lane agrees, and adds that a more logical approach would be to control appetite in the brain.

The National Heart, Lung and Blood Institute can help you aim for a healthy weight.

For general information on excess weight and obesity, visit the American Obesity Association or the American Dietetic Association.

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