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Genetics - Obesity & DNA
A Gene to Eat More, Weigh Less?
Last updated: Monday, January 17, 2005
Everything's bigger in Texas, except the mice. And that could be good news for overweight people.

Researchers in Texas say they've bred a strain of lab mice that have half the body fat of normal animals and can eat up to 40 percent more than regular rodents without gaining an ounce.

 
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The animals lack the gene for an enzyme that governs the conversion of fat into energy.

Blocking the same enzyme in humans, the researchers say, could lead to the development of a drug to promote weight loss and prevent obesity.

"The couch potato guys could sit and enjoy their potato chips and watch television and not have to run" to shed pounds, says study co-author Dr. Salih Wakil, a biochemist at the Baylor College of Medicine in Houston. The finding appears in this week's issue of Science.

When an animal eats, it converts some of the nutrients into short-term energy and stashes other compounds away for a lean day. Fat stores become the body's molecular pantry.

Two related enzymes control fat storage and burning - ACC1 and ACC2, for acetyl-CoA carboxylase 1 and 2. Both produce another molecule, malonyl-CoA, which, depending on its location in the cell, directs the accumulation or breakdown of fatty acids.

Mice embryos missing ACC1 die after about a week in the womb, suggesting that fat storage is indispensable to life, the researchers say.

But mice missing ACC2 have a much different fate. The study shows the mutant animals make dramatically less malonyl-CoA in fat-amassing cell sites than normal mice - 10 times less in their heart tissue and 30 times less in muscle.

Yet, while their cells convert fat into energy at an intense clip, they seem otherwise fine.

"The mice seem to be happy, breed well and after two years are OK," Wakil says.

More than OK, in fact, from a dieter's perspective.

Animals lacking ACC2 have a hearty appetite, consuming 20 percent to 40 percent more food than their genetically normal cage-mates, yet they weigh 10 percent to 15 percent less. Their body fat content is half that of wild mouse strains, the study says.

Dr Roger Brownsey, a biochemist at the University of British Columbia who studies the ACC enzyme, says he's "not at all surprised" by the Texas findings.

"Unlocking the inhibition of fatty acid oxidation [is something] you would expect [would] have a profound effect on overall energy balance," Brownsey says. And the approach certainly could apply to help obese people slim down, he says.

Still, whether the storage of excess fat is the cause of people's obesity, or whether an earlier mechanism leads to the accumulation of fatty acids, he says, is not clear.


 
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