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Lab creates an all-it-can-eat mouse

A UC Berkeley team finds that knocking out a key gene, DNA-PK, prevents weight gain from carbs.

March 21, 2009|Melissa Healy

Imagine you've bellied up to the all-you-can-eat pasta bar in Berkeley, only to meet one of the mice from Hei Sook Sul's Nutritional Science and Toxicology Lab.

If you come here often, you know that loading up on carbohydrates is going to make you pretty chubby. But you notice that your fellow diner -- the mouse -- is pretty slim. How does he do it?

This lucky mouse has had a gene knocked out of his genome by researchers in Sul's UC Berkeley lab. The observation that mice without this gene can eat all the carbs they want and stay slim -- whereas other mice fed a high-carb diet become fat -- leads Sul to conclude that her lab has found a gene that plays a key role in the process of converting carbohydrates to fat. And that discovery points to an important new target for drug developers hoping to find a way to prevent and perhaps even reverse obesity in humans.

The discovery of the gene's role in obesity was published Friday in the journal Cell.

The gene involved, known as DNA-PK (for DNA-dependent protein kinase), is widely studied for its role in repairing breaks in the DNA -- a function that has made it crucial in cancer research and treatment. But Sul said it was a surprise to discover that the same gene has a key role in the liver's conversion of excess glucose (all that bread, pasta and sugary soda you've failed to work off) to fatty acids.

Not only were mice whose DNA-PK gene had been knocked out 40% leaner than normal mice when all were fed a high-carb, low-fat diet; they also had better blood-lipid profiles, suggesting they'd be at lower risk of developing heart disease.

Sul said no one at this point was thinking about gene therapy as a treatment for obesity. Instead, drug developers might look at how the DNA-PK gene calls out other actors to set in motion the conversion of excess calories to fat and find an agent that might disrupt the process.

If they're successful, you'll be able to join that mouse at the pasta bar and look just as svelte as he does.

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melissa.healy@latimes.com

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