Worms offer the skinny on fat genes

Microscopic worms that feasted on genetically engineered bacteria might shed light on why people gain weight. Biologists used this bacterial diet plan to turn off individual genes in the worms in order to identify ones that influence the animal’s fat.

Investigators recently engineered around 17,000 strains of the bacterium Escherichia coli so that each strain makes an extra RNA strand that corresponds to a specific worm gene. When a worm consumes a particular E. coli strain, the additional RNA shuts down the corresponding worm gene through a phenomenon called RNA interference (SN: 10/19/02, p. 254: Bacterial diet quiets worm genes).

Gary Ruvkun of Massachusetts General Hospital in Boston and his colleagues used this library of bacterial strains to search for worm genes that could reflect human genes involved in obesity. With the help of a dye that marks fat droplets in living worms, the scientists monitored the fat storage of worms as they gobbled up the various E. coli strains. Through this strategy, the scientists inactivated genes one by one and found 305 cases in which the RNA-fed worms stored more fat and 112 instances in which they stored less.

Of the 417 fat-regulating genes thus identified, about 100 have known human counterparts, Ruvkun’s group reports in the Jan. 16 Nature. Some of these genes have previously been implicated in human obesity, but most haven’t. These latter genes “may point to ancient and universal features of fat-storage regulation and identify targets for treating obesity and its associated diseases,” the researchers conclude.

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