As C . elegans is an excellent model for many biological

For example, serotonin 5-HT2C receptor knockout mice To gain insights into the genetic cascades that reguand worms lacking serotonin signaling accumulate exlate fat biology, we evaluated C. elegans as an approcess fat (Sze et al., 2000; Nonogaki et al., 1998). Insulin priate model organism. We generated worms that lack signaling is a primary mechanism for controlling metatwo transcription factors, SREBP and C/EBP, crucial bolic physiology not only in humans, but also in worms for formation of mammalian fat. Worms deficient in (Kimura, 1997). In addition, worms have homologs of either of these genes displayed a lipid-depleted phemany mammalian lipogenic and lipolytic enzymes (C. notype—pale, skinny, larval-arrested worms that lack elegans Sequencing Consortium, 1998). Worms also fat stores. On the basis of this phenotype, we used a contain homologs of the transcription factors C/EBP reverse genetic screen to identify several additional and SREBP (see below), which regulate mammalian adigenes that play a role in worm lipid storage. Two of pocyte differentiation (Rosen et al., 2000). C. elegans the genes encode components of the mitochondrial therefore contains homologs of genes encompassing a respiratory chain (MRC). When the MRC was inhibited wide range of components of the mammalian fat regulachemically in worms or in a mammalian adipocyte tory cascade, including hormonal regulators, differentiamodel, fat accumulation was markedly reduced. A tion factors, and biosynthetic enzymes. third encodes lpd-3, whose homolog is also required There are some potential problems with using worms for fat storage in a mammalian model. These data as a model for fat biology. In worms, the intestine, an suggest that C. elegans is a genetically tractable endodermal derivative, is the major site of energy stores, model to study the mechanisms that underlie the biolwhich are contained in several types of gut granules; ogy of fat-storing tissues. some contain protein and carbohydrate, while others