CGC Bibliography Paper 5707

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

McKay RM, McKay JP, Avery L, Graff JM

Medline:

12530969

Citation:

Developmental Cell 4: 131-142 2003

Type:

ARTICLE

Genes:

eat-2 mac-1 lpd-1 lpd-2 lpd-3 lpd-4 lpd-5 lpd-6 lpd-7 lpd-8 lpd-9

Abstract:

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