Gene That Can Stop Mice from Becoming Obese Identified

Researchers have found a gene that when blocked can keep mice from becoming obese, even if they consume a high-fat diet, new research released Thursday found.

The gene, dubbed IKKE, acts as the main control center for obesity in the lab animals. When it is successfully blocked, mice remain thin even if they are devouring high-fat foods, said Alan Saltiel, director of the University of Michigan's Life Science Institute.

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If further research shows IKKE is tied to obesity in humans, the gene and the protein it makes will be key targets for developing drugs to treat obesity, diabetes and related complications, he added.

"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," said Saltiel, lead author of the paper appearing in the September 4 edition of the journal Cell.

"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," he said.

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Some of the mice ate a diet in which 45 percent of the calories were from fat.

Another group ate regular chow with 4.5 percent fat content.

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They started the diets at eight weeks and continued through 14 to 16 weeks of age.

The gene IKKE produces a protein kinase, which also is called IKKE. Protein kinases are enzymes that effectively "turn on or off" other proteins. The IKKE protein kinase appears to target proteins which, in turn, control genes that regulate mouse metabolism.

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When normal mice were on the high-fat diet, IKKE protein-kinase levels rose, the metabolic rate slowed, and the animals gained weight. Here the IKKE protein kinase acts as a brake on the metabolism, researchers said.

Meanwhile, mice on the high-fat diet did not gain weight, "apparently because deleting the IKKE gene releases the metabolic brake, allowing it to speed up and burn more calories, instead of storing those calories as fat," they added in a statement.

Saltiel's team is now searching for small molecules that block IKKE protein-kinase activity. IKKE inhibitors could become candidates for drug development, they said.

"If you find an inhibitor of this protein kinase, you should be able to obtain the same effect as knocking out the gene. And that's the goal," Saltiel said.

New treatments for obesity and diabetes -- if successful candidates are identified and drug development carried out -- may be a decade down the line, he said.

Source-AFP
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