Expression profiling of HNF4-dependent transcripts in Drosophila larvae

We show 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. HNF4 dependent transcripts were identified under fed and starved conditions. Microarray studies indicate reduced expression of genes that control lipid catabolism and beta-oxidation. Late second instar control and HNF4 mutant larvae were collected and fed or starved for 24 hours, and then RNA was isolated for analysis. 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.

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