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PMID:19254568

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Citation

Palanker, L, Tennessen, JM, Lam, G and Thummel, CS (2009) Drosophila HNF4 regulates lipid mobilization and beta-oxidation. Cell Metab. 9:228-39

Abstract

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.

Links

PubMed PMC2673486 Online version:10.1016/j.cmet.2009.01.009

Keywords

Animals; Caenorhabditis elegans/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/anatomy & histology; Drosophila melanogaster/physiology; Energy Metabolism; Fatty Acids/metabolism; Gene Expression Profiling; Hepatocyte Nuclear Factor 4/genetics; Hepatocyte Nuclear Factor 4/metabolism; Humans; Lipid Mobilization; Oligonucleotide Array Sequence Analysis; Oxidation-Reduction; Starvation; Tissue Distribution; Triglycerides/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:HNF4

involved_in

GO:0016042: lipid catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:HNF4

involved_in

GO:0034440: lipid oxidation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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