Journal
DEVELOPMENTAL CELL
Volume 48, Issue 2, Pages 200-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2018.11.030
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Funding
- NIH [S10 OD016232-01, S10 OD021505-01, U54 DK110858-01, R01DK108941]
- Fondation pour la Recherche Medicale [FRM SPE 40181]
- Bettencourt Schueller Foundation
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Animals must adjust their metabolism as they progress through development in order to meet the needs of each stage in the life cycle. Here, we show that the dHNF4 nuclear receptor acts at the onset of Drosophila adulthood to direct an essential switch in lipid metabolism. Lipid stores are consumed shortly after metamorphosis but contribute little to energy metabolism. Rather, dHNF4 directs their conversion to very long chain fatty acids and hydrocarbons, which waterproof the animal to preserve fluid homeostasis. Similarly, HNF4 alpha is required in mouse hepatocytes for the expression of fatty acid elongases that contribute to a waterproof epidermis, suggesting that this pathway is conserved through evolution. This developmental switch in Drosophila lipid metabolism promotes lifespan and desiccation resistance in adults and suppresses hallmarks of diabetes, including elevated glucose levels and intolerance to dietary sugars. These studies establish dHNF4 as a regulator of the adult metabolic state.
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