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Scientists Turn Off 'Obesity Switch' in Mice

Deleted gene allows rodents to eat high-fat diet and stay thin, research shows

THURSDAY, Sept. 3, 2009 (HealthDay News) -- Researchers have found a gene that, when switched off, enables mice to stay slender -- even those who eat fatty diets.

When scientists deleted the IKKE gene from mice, they found that the rodents no longer gained weight even when fed a lard-like substance instead of their usual low-fat chow.

"We've studied other genes associated with obesity -- we call them 'obesogenes' -- but this is the first one we've found that, when deleted, stops the animal from gaining weight," senior study author Alan Saltiel, the Mary Sue Coleman Director of the University of Michigan Life Sciences Institute, said in a university news release.

In the study, which is published in the Sept. 4 issue of the journal Cell, some mice ate diets with 45 percent of calories from fat, while others ate diets with 4.5 percent of calories from fat for 14 to 16 weeks. The mice with the deleted IKKE gene that were on the high-fat diet stayed slender.

The researchers believe that deleting the IKKE gene speeds the metabolism of mice, enabling them to burn more calories instead of storing them as fat.

The IKKE gene produces a protein kinase, or enzyme that activates other proteins, also named IKKE. Researchers believe that the IKKE protein kinase targets proteins that control genes that regulate metabolism.

When normal mice are fed a high-fat diet, IKKE protein-kinase levels rise, slowing the metabolic rate and causing weight gain. This doesn't happen in mice with the IKKE gene "knocked out," the study authors noted.

"The knockout mice are not exercising any more than the control mice used in the study. They're just burning more energy," Saltiel said. "And in the process, they're generating a little heat, as well -- their body temperature actually increases a bit."

Obesity is associated with chronic, low-grade inflammation that can lead to insulin resistance, a precursor to type 2 diabetes. Not only did the mice with the deleted IKKE gene avoid weight gain, they showed no signs of chronic inflammation, fatty liver or insulin resistance either, according to the study.

Follow-up research is needed to determine if IKKE plays a role in weight gain in humans. If so, there's the potential to develop anti-obesity drugs that would target the gene and its protein.

"The fact that you can disrupt all the effects of a high-fat diet by deleting this one gene in mice is pretty interesting and surprising," Saltiel said.

More information

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases has more on obesity.

SOURCE: University of Michigan, news release, Sept. 3, 2009
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