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Humans and worms share genes involved in storing fat
By Adam Marcus

In a finding that could one day aid the treatment of obesity and its opposite, anorexia, scientists have found that worms and humans share about 150 genes involved in storing fat. Some of the genes identified in the study were not previously known to play a role in body weight.

C. elegans

The researchers analyzed all 16,757 genes in the worm C. elegans, whose genome has been sequenced. They identified about 400 that help regulate how fat is stored and used. Next, they found that about 150 of these have counterparts in humans.

"Our knowledge about how fat is regulated is still relatively limited," says Gary Ruvkun, a geneticist at Harvard Medical School in Boston, who led the research. "These are early days still." He predicts that only a fraction of the human genes implicated in this study may turn out to be targets for treating obesity in people.

Jonathan M. Graff, a developmental biologist at the University of Texas Southwestern Medical Center in Dallas, who studies fat genes in C. elegans, calls the research "beautiful."

The work, he says, will help researchers identify the genetic underpinnings of how fat cells are made, along with the proteins involved. Some of these proteins may be excellent targets for drugs to help people with diabetes, obesity and other conditions associated with the buildup of excess fat.

Ruvkun's team used a technique called RNA interference to identify genes involved in regulating fat storage in the worm. The technique involves giving the worm RNA molecules, which effectively silence one gene per worm. For each 'silenced' gene, the researchers determined whether the worm had more or less fat.

In one 'gene therapy' experiment, the researchers added fat-suppressing genes to overweight worms, such as a mutant strain called 'tubby.' Roughly 70 of the genes cured every obese syndrome the researchers tested, according to findings published in Nature.

The functions of many of the worm genes that Ruvkun studied have been described previously. Some help cells create long fatty-acid molecules or stitch together their fatty outer membranes, for example. Inhibiting these genes should, and does, reduce fat storage.

However, the researchers say, they were surprised to find that when they mutated a gene that burns fat, the worm seemed to store less fat. This suggests that worms have a complex feedback system that researchers don't yet understand, says Ruvkun.

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Ashrafi, K. et al. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268-72 (January 16, 2003).
McKay, R. M. et al. C. elegans. A model for exploring the genetics of fat storage. Dev Cell 4, 131-142 (January 2003).

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