Document Detail


Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs.
MedLine Citation:
PMID:  12032166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. In the process of searching for genes activated by sterol regulatory element-binding protein 1 (SREBP-1) by using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar to a fatty acyl-CoA elongase gene family such as Cig30, Sscs, and yeast ELOs. Studies on the cells overexpressing the full-length cDNA indicate that the encoded protein, designated fatty acyl-CoA elongase (FACE), has a FACE activity specific for long-chains; C12-C16 saturated- and monosaturated-fatty acids. Hepatic expression of this identified gene was consistently activated in the livers of transgenic mice overexpressing nuclear SREBP-1a, -1c, or -2. FACE mRNA levels are markedly induced in a refed state after fasting in the liver and adipose tissue. This refeeding response is significantly reduced in SREBP-1 deficient mice. Dietary PUFAs caused a profound suppression of this gene expression, which could be restored by SREBP-1c overexpression. Hepatic FACE expression was also highly up-regulated in leptin-deficient ob/ob mice. Hepatic FACE mRNA was markedly increased by administration of a pharmacological agonist of liver X-activated receptor (LXR), a dominant activator for SREBP-1c expression. These data indicated that this elongase is a new member of mammalian lipogenic enzymes regulated by SREBP-1, playing an important role in de novo synthesis of long-chain saturated and monosaturated fatty acids in conjunction with fatty acid synthase and stearoyl-CoA desaturase.
Authors:
Takashi Matsuzaka; Hitoshi Shimano; Naoya Yahagi; Tomohiro Yoshikawa; Michiyo Amemiya-Kudo; Alyssa H Hasty; Hiroaki Okazaki; Yoshiaki Tamura; Yoko Iizuka; Ken Ohashi; Jun-Ichi Osuga; Akimitsu Takahashi; Shigeru Yato; Hirohito Sone; Shun Ishibashi; Nobuhiro Yamada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of lipid research     Volume:  43     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-28     Completed Date:  2003-01-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  911-20     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acyl Coenzyme A / metabolism*
Amino Acid Sequence
Animals
Base Sequence
CCAAT-Enhancer-Binding Proteins / metabolism*
Cell Line
Cloning, Molecular
DNA, Complementary
DNA-Binding Proteins / metabolism*
Fatty Acids, Unsaturated / metabolism
Gene Expression Regulation, Enzymologic
Humans
Ligands
Liver / metabolism*
Mice
Mice, Transgenic
Molecular Sequence Data
Nutritional Physiological Phenomena
Sequence Alignment
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Substrate Specificity
Tissue Distribution
Transcription Factors / metabolism*
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/CCAAT-Enhancer-Binding Proteins; 0/DNA, Complementary; 0/DNA-Binding Proteins; 0/Fatty Acids, Unsaturated; 0/Ligands; 0/SREBF1 protein, human; 0/SREBF2 protein, human; 0/Srebf1 protein, mouse; 0/Srebf2 protein, mouse; 0/Sterol Regulatory Element Binding Protein 1; 0/Sterol Regulatory Element Binding Protein 2; 0/Transcription Factors

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