Scientists at Massachusetts General Hospital (MGH) and their colleagues have scoured thousands of genes in the C. elegans worm and have come up with hundreds of promising candidates that may determine how fat is stored and used in a variety of animals. The findings, published in the Jan. 16 issue of Nature, represent the first survey of an entire genome for all genes that regulate fat storage.

The research team led by Gary Ruvkun, PhD, of the MGH Department of Molecular Biology, and postdoctoral fellow Kaveh Ashrafi, PhD, identified about 400 genes encompassing a wide range of biochemical activities that control fat storage. These studies were conducted using the tiny roundworm Caenorhabditis elegans, an organism that shares many genes with humans and has helped researchers gain insights into diseases as diverse as cancer, diabetes, and Alzheimer's disease.

Many of the fat regulatory genes identified in this study have counterparts in humans and other mammals. "This study is a major step in pinpointing fat regulators in the human genome," says Ruvkun, who is a professor of Genetics at Harvard Medical School. "Of the estimated 30,000 human genes, our study highlights about 100 genes as likely to play key roles in regulation of fat levels," he continued. Most of these human genes had not previously been predicted to regulate fat storage. This prediction will be tested as obese people are surveyed for mutations in the genes highlighted by this systematic study of fat in worms.

In addition, this study points to new potential therapies for obesity. Inactivation of about 300 worm genes causes worms to store much less fat than normal. Several of the human counterparts of these genes encode proteins that are attractive for the development of drugs. Thus, the researchers suggest that some of the genes identified could point the way for designing drugs to treat obesity and its associated diseases such as diabetes.

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Contact: Susan McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
15-Jan-2003

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