Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susc
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Cellular and Molecular Life Sciences
ORIGINAL ARTICLE
Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation Stefan Schäbler1 · Kelechi M. Amatobi1 · Melanie Horn2 · Dirk Rieger2 · Charlotte Helfrich‑Förster2 · Martin J. Mueller1 · Christian Wegener2 · Agnes Fekete1 Received: 14 March 2019 / Revised: 27 November 2019 / Accepted: 23 December 2019 © The Author(s) 2020
Abstract The fruit fly Drosophila is a prime model in circadian research, but still little is known about its circadian regulation of metabolism. Daily rhythmicity in levels of several metabolites has been found, but knowledge about hydrophobic metabolites is limited. We here compared metabolite levels including lipids between period01 (per01) clock mutants and Canton-S wildtype (WTCS) flies in an isogenic and non-isogenic background using LC–MS. In the non-isogenic background, metabolites with differing levels comprised essential amino acids, kynurenines, pterinates, glycero(phospho)lipids, and fatty acid esters. Notably, detectable diacylglycerols (DAG) and acylcarnitines (AC), involved in lipid metabolism, showed lower levels in per01 mutants. Most of these differences disappeared in the isogenic background, yet the level differences for AC as well as DAG were consistent for fly bodies. AC levels were dependent on the time of day in WTCS in phase with food consumption under LD conditions, while DAGs showed weak daily oscillations. Two short-chain ACs continued to cycle even in constant darkness. per01 mutants in LD showed no or very weak diel AC oscillations out of phase with feeding activity. The low levels of DAGs and ACs in per01 did not correlate with lower total food consumption, body mass or weight. Clock mutant flies showed higher sensitivity to starvation independent of their background-dependent activity level. Our results suggest that neither feeding, energy storage nor mobilisation is significantly affected in per01 mutants, but point towards impaired mitochondrial activity, supported by upregulation of the mitochondrial stress marker 4EBP in the clock mutants. Keywords Circadian rhythms · Metabolomics · Mitochondrial activity · Tryptophan · Acylcarnitine · Feeding
Introduction Stefan Schäbler and Kelechi M. Amatobi contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00018-019-03441-6) contains supplementary material, which is available to authorized users. * Christian Wegener [email protected]‑wuerzburg.de * Agnes Fekete agnes.fekete@uni‑wuerzburg.de 1
Pharmaceutical Biology, Julius‑Von‑Sachs‑Institute, Biocenter, University of Würzburg, Julius‑von‑Sachs Platz 2, 97084 Würzburg, Germany
Neurobiology and Genetics, Würzburg Insect Research, Theodor‑Boveri‑Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany
2
The interaction between circadian clocks and metabolism is of increasing interest, since clock d
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