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Specialized hepatocyte-like cells regulate Drosophila lipid metabolism

Abstract

Lipid metabolism is essential for growth and generates much of the energy needed during periods of starvation. In Drosophila, fasting larvae release large quantities of lipid from the fat body but it is unclear how and where this is processed. Here we identify the oenocyte as the principal cell type accumulating lipid droplets during starvation. Tissue-specific manipulations of the Slimfast amino-acid channel, the Lsd2 fat-storage regulator and the Brummer lipase indicate that oenocytes act downstream of the fat body. In turn, oenocytes are required for depleting stored lipid from the fat body during fasting. Hence, lipid-metabolic coupling between the fat body and oenocytes is bidirectional. When food is plentiful, oenocytes have critical roles in regulating growth, development and feeding behaviour. In addition, they specifically express many different lipid-metabolizing proteins, including Cyp4g1, an ω-hydroxylase regulating triacylglycerol composition. These findings provide evidence that some lipid-processing functions of the mammalian liver are performed in insects by oenocytes.

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Figure 1: Oenocytes accumulate lipids during starvation.
Figure 2: The fat body regulates lipid accumulation in oenocytes.
Figure 3: Oenocytes regulate growth and developmental progression.
Figure 4: Oenocytes are required for lipid depletion from the fat body during starvation.
Figure 5: Cyp4g1 is an essential oenocyte-specific gene regulating TAG composition.

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Acknowledgements

We thank G. Gibbons and K. Frayn for providing advice and facilities for metabolic profiling, and P. Elstob, V. Brodu, S. Mahadevaiah and P. Sarchet for assistance with enhancer trap screening and sequencing. We also thank S. Celniker and BDGP for providing many of the panels used in Supplementary Fig. 4, and R. Barrio, B. Bello, L. Michaut, A. Brand, R. Carthew, W. Janning, S. Kennel, C. O’Kane, R. Kühnlein, P. Leopold, I. Miguel-Aliaga, I. Salecker, R. Schultz, N. Tapon, C. Thummel, J.-P. Vincent, T. Xu, Flyview, The NP consortium, the DGRC at Kyoto Institute of Technology, the Bloomington, Umeå, and Szeged stock centres and the DSHB at the University of Iowa for DNA constructs, flies and antibodies. We also thank I. Robinson for discussions and J. Briscoe, X. Franch-Marro, G. Gibbons, I. Miguel-Aliaga, E. Ober, E. Piddini, I. Salecker, P. Serpente and D. Wilkinson for critical reading of the manuscript. This work was supported by the Medical Research Council (E.G., D.W and A.P.G.), the Mexican National Council for Science and Technology (E.G.) and the Wellcome Trust (B.F.).

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Correspondence to Alex P. Gould.

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Gutierrez, E., Wiggins, D., Fielding, B. et al. Specialized hepatocyte-like cells regulate Drosophila lipid metabolism. Nature 445, 275–280 (2007). https://doi.org/10.1038/nature05382

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