C elegans: a model for exploring the genetics of fat storage.

To gain insights into the genetic cascades that regulate fat biology, we evaluated C. elegans as an appropriate model organism. We generated worms that lack two transcription factors, SREBP and C/EBP, crucial for formation of mammalian fat. Worms deficient in either of these genes displayed a lipid-depleted phenotype-pale, skinny, larval-arrested worms that lack fat stores. On the basis of this phenotype, we used a reverse genetic screen to identify several additional genes that play a role in worm lipid storage. Two of the genes encode 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 encodes lpd-3, whose homolog is also required for fat storage in a mammalian model. These data suggest that C. elegans is a genetically tractable model to study the mechanisms that underlie the biology of fat-storing tissues.