Document Detail


Drosophila HNF4 regulates lipid mobilization and beta-oxidation.
MedLine Citation:
PMID:  19254568     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Drosophila HNF4 (dHNF4) is the single ancestral ortholog of a highly conserved subfamily of nuclear receptors that includes two mammalian receptors, HNFalpha and HNFgamma, and 269 members in C. elegans. We show here that dHNF4 null mutant larvae are sensitive to starvation. Starved mutant larvae consume glycogen normally but retain lipids in their midgut and fat body and have increased levels of long-chain fatty acids, suggesting that they are unable to efficiently mobilize stored fat for energy. Microarray studies support this model, indicating reduced expression of genes that control lipid catabolism and beta-oxidation. A GAL4-dHNF4;UAS-lacZ ligand sensor can be activated by starvation or exogenous long-chain fatty acids, suggesting that dHNF4 is responsive to dietary signals. Taken together, our results support a feed-forward model for dHNF4, in which fatty acids released from triglycerides activate the receptor, inducing enzymes that drive fatty acid oxidation for energy production.
Authors:
Laura Palanker; Jason M Tennessen; Geanette Lam; Carl S Thummel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  9     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-03     Completed Date:  2009-03-30     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  228-39     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Caenorhabditis elegans / metabolism
Drosophila Proteins / genetics,  metabolism*
Drosophila melanogaster* / anatomy & histology,  physiology
Energy Metabolism
Fatty Acids / metabolism*
Gene Expression Profiling
Hepatocyte Nuclear Factor 4 / genetics,  metabolism*
Humans
Lipid Mobilization*
Oligonucleotide Array Sequence Analysis
Oxidation-Reduction
Starvation
Tissue Distribution
Triglycerides / metabolism*
Grant Support
ID/Acronym/Agency:
R01 DK075607/DK/NIDDK NIH HHS; R01 DK075607-03/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Drosophila Proteins; 0/Fatty Acids; 0/Hepatocyte Nuclear Factor 4; 0/Triglycerides
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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