Even the Worm Has Hundreds of Fat Storage Genes
Wed Jan 15, 5:39 PM ET By Alison McCook
NEW YORK (Reuters Health) - A tiny worm often used as a model to study human genetic diseases carries 417 genes that help control how much fat is stored in the body, research released Wednesday shows.
Around 200 of the 400 genes linked to fat storage in the worm appear to have a counterpart in humans.
The next step is to determine whether people who are obese carry altered forms of these genes. If that proves to be the case, some of those genes could be targets for anti-obesity drugs, study author Dr. Gary Ruvkun of Massachusetts General Hospital and Harvard University in Boston told Reuters Health.
The findings suggest that fat storage is a complicated process influenced by many different substances in the body, Ruvkun said.
The species of worm is Caenorhabditis elegans, or C. elegans, and holds the honor of being the first organism to have its entire genetic makeup decoded.
While the roundworm is only about 1 millimeter long and lives a few weeks at best, it shares many of its genes with humans. Therefore, scientists can study the worm genome for clues to human disease.
Researchers estimate the worm carries almost 20,000 genes that code for substances in the body.
In two papers published in the January 16 issue of Nature, an international group of researchers describe a procedure used to determine the function of each gene in C. elegans, and pinpoint the genes that help regulate body fat storage.
In an interview with Reuters Health, Ruvkun explained that he and his colleagues discovered which genes were involved in obesity by engineering the worms' food so that it included substances that knocked out a particular gene. The food also contained dye that colored all body fat. The worms are transparent, Ruvkun explained, so researchers could simply look at a worm and see how much fat it contained.
In his paper, Ruvkun and his colleagues report that 305 genes, when knocked out, appeared to make the worms thinner. Another 112 genes appeared to increase body fat when inactivated.
In humans, the number of genes linked to fat absorption could form a "much expanded list," Ruvkun said, given that humans have more genes than C. elegans. This high number suggests that the process of adding and subtracting body fat is complex, he noted, and likely involves more than the activity of one or two substances, such as the newly discovered "hunger hormone" ghrelin and the "obesity hormone" leptin.
There is an "art" to picking out the most promising targets for new drugs, because investigating whether a substance works as a drug target is a time-consuming and expensive process, Ruvkun added. "Not all proteins are equally good targets for drug development," he said. Having a list of 200 to choose from might make the process easier, he noted.
Ruvkun said that he suspected 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.
SOURCE: Nature 2003;421:231-237,268-272,220-221. |
