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PMID: 12530969 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Developmental cell ·Vol. 4 ·No. 1 ·2003-01-00 ·Pages 131-42

McKay RM, McKay JP, Avery L, Graff JM

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.

MeSH Terms
3T3 Cells Adipose Tissue/metabolism Animals CCAAT-Enhancer-Binding Proteins/genetics,metabolism Caenorhabditis elegans/genetics,metabolism Caenorhabditis elegans Proteins/genetics DNA-Binding Proteins/genetics,metabolism Eating Electron Transport/genetics Gene Expression Regulation Genes, Helminth/genetics Humans Intestinal Mucosa/metabolism Larva/genetics,metabolism Lipid Metabolism Mammals/genetics,metabolism Mice Mitochondria/metabolism Models, Animal Mutation Phenotype RNA, Messenger/genetics,metabolism Starvation/metabolism Sterol Regulatory Element Binding Protein 1 Transcription Factors
Chemicals
CCAAT-Enhancer-Binding Proteins Caenorhabditis elegans Proteins DNA-Binding Proteins RNA, Messenger SREBF1 protein, human Srebf1 protein, mouse Sterol Regulatory Element Binding Protein 1 Transcription Factors lpd-3 protein, C elegans
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
McKay Renée M
Center for Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
McKay James P
Avery Leon
Graff Jonathan M
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
DOI
10.1016/s1534-5807(02)00411-2
Published
2003-01-00
Pages
131-42
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC4445237
Subset
IM
Grants
NHLBI NIH HHS · 5-T32-HL07360 · United States
NIDDK NIH HHS · R01 DK064261 · United States
NHLBI NIH HHS · T32 HL007360 · United States
NICHD NIH HHS · F32 HD08609-01 · United States
NICHD NIH HHS · F32 HD008609 · United States
External Links
PubMed source DOI: 10.1016/s1534-5807(02)00411-2 PMC Full Text View journal details
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