title: C elegans: a model for exploring the genetics of fat storage.
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 tissues.
authors.affiliation: Center for Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Renée M
authors.initials: RM
authors.lastname: McKay
authors.forename: James P
authors.initials: JP
authors.lastname: McKay
authors.forename: Leon
authors.initials: L
authors.lastname: Avery
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Graff
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004435:Eating; D004579:Electron Transport / Q000235:genetics; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013217:Starvation / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C471933:lpd-3 protein, C elegans