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Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes
Author(s): Ashrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS, Ahringer J, Ruvkun G
Source: NATURE    Volume: 421    Issue: 6920    Pages: 268-272    Published: JAN 16 2003  
Times Cited: 347     References: 29     
Abstract: Regulation of body fat storage involves signalling between centres that regulate feeding in the brain and sites of fat storage and use in the body(1,2). Here we describe an assay for analysing fat storage and mobilization in living Caenorhabditis elegans. By using RNA-mediated interference (RNAi)(3,4) to disrupt the expression of each of the 16,757 worm genes, we have systematically screened the C. elegans genome for genes necessary for normal fat storage. We identify 305 gene inactivations that cause reduced body fat and 112 gene inactivations that cause increased fat storage. Analysis of the fat-reducing gene inactivations in insulin, serotonin and tubby signalling mutants of C. elegans, which have increased body fat, identifies a core set of fat regulatory genes as well as pathway-specific fat regulators. Many of the newly identified worm fat regulatory genes have mammalian homologues, some of which are known to function in fat regulation. Other C. elegans fat regulatory genes that are conserved across animal phylogeny, but have not previously been implicated in fat storage, may point to ancient and universal features of fat storage regulation, and identify targets for treating obesity and its associated diseases.
Document Type: Article
Language: English
Reprint Address: Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
Addresses:
1. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
2. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
3. Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA
4. Univ Cambridge, Wellcome Canc Res UK Inst, Cambridge CB2 1QR, England
Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Subject Category: Multidisciplinary Sciences
IDS Number: 635KG
ISSN: 0028-0836
DOI: 10.1038/nature01279
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