Roundworms Provide Hints on Obesity

With a discovery on the genetic composition of roundworms, scientists have come closer to finding new methods for treating obesity.

Gary Ruvkun, professor of genetics at Harvard Medical School, used a promising new technique to identify about 417 genes in the roundworm’s genetic code related to fat production and storage.

With the help of his team of scientists, Ruvkun—whose results were published in last Thursday’s issue of the journal Nature—deactivated about 305 of the genes in the experiment, resulting in “thin and happy” bioengineered worms.

But when his team deactivated the remaining 112 genes, the worms grew fatter.

By using a novel gene identification method developed in England’s Wellcome Trust/Cancer Research UK Institute, the research team discovered that around 200 of the 400 genes linked to fat storage in worms appear to have a counterpart in humans.

“If someone told me we’d be using this kind of protocol even three years ago, I’d have said that’s crazy—don’t think about it,” Ruvkun said.

More research will aim to determine whether people who are obese carry altered forms of these genes. If that proves to be the case, then some of those genes could be targets for anti-obesity drugs.

Statistics show that one in five Americans is obese, and this condition contributes to conditions like diabetes and heart failure.

The worm species, Caenorhabditis elegans, or C. elegans, measures 1/25th of an inch long with a smooth cylinder-shaped body tapered at both ends and lives a few weeks at most.

It is the first organism to have its entire genetic makeup decoded, and has been widely used by scientists in their experiments because of its simplicity and belief that humans share a common ancestry.

Ruvkun and his team discovered which genes were related to obesity by engineering the worms’ food to include substances that deactivated a particular gene.

Since the worms are transparent and their food also contained dye that colored the body fat, researchers could simply look at a worm and see how much fat it contained.

Humans share about half the roundworm’s 20,000 genes, including 200 of the fat-storage genes, but whether the same gene deactivation technique will work out in humans is still unclear.

Ruvkun suggests that with the current understanding of the roundworm’s gene composition, new drugs might be developed to deal with obesity.

But he said the number of genes linked to fat absorption in humans might be much longer and form a more complex system within the body.

With 200 proteins to choose from as targets for possible anti-obesity drugs, scientists will not have an easy time because investigating whether a substance works as a drug target is a time-consuming and expensive process.

“Not all proteins are equally good targets for drug development,” said Ruvkun.

He said that within the next few years, drug developers may have narrowed their options for new drug targets to approximately 10 proteins linked to fat absorption.