Nematode Worms Help Explain Genetics of Obesity

In a recent study, researchers used the nematode worm C elegans as a model for exploring the genetic basis for obesity in humans. Their findings appeared in the January 2003 issue of Developmental Cell.

The investigators, from the University of Texas Southwestern Medical Center (Dallas, USA; www.utsouthwestern.edu), generated worms that lacked two transcription factors, SREBP and C/EBP, crucial for formation of mammalian fat. Worms deficient in either of these genes display a lipid-depleted phenotype—pale, skinny, larval-arrested worms that lack fat stores.

On the basis of this phenotype, the researchers employed a reverse genetic screen to identify several additional genes that played a role in worm lipid storage. Two of the genes encoded components of the mitochondrial respiratory chain (MRC). When the MRC was inhibited chemically in worms or in a mammalian adipocyte model, fat accumulation was markedly reduced. A third gene encoded lpd-3, whose homolog is also required for fat storage in mammals.

"Obesity and its associated diseases are now among the most important medical conditions in the world,” explained senior author Dr. Jonathan M. Graff, associate professor in the Center for Developmental Biology at UT Southwestern. "A billion people in the world are overweight, and during the next few decades, it will be one of the major health issues facing mankind. The alarming increase in obesity highlights the critical need to identify genes that are involved in regulating fat-cell development and function.”



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Univ. of Texas Southwestern Medical Center