Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-232432
- 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 period\(^{01}\) (per\(^{01}\)) clock mutants and Canton-S wildtype (WT\(_{CS}\)) flies in an isogenic and non-isogenic background using LC–MS. In the non-isogenic background, metabo-lites with differing levels comprised essentialThe 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 period\(^{01}\) (per\(^{01}\)) clock mutants and Canton-S wildtype (WT\(_{CS}\)) flies in an isogenic and non-isogenic background using LC–MS. In the non-isogenic background, metabo-lites 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 per\(^{01}\) 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. per\(^{01}\) 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 per\(^{01}\) 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 per\(^{01}\) mutants, but point towards impaired mitochondrial activity, supported by upregulation of the mitochondrial stress marker 4EBP in the clock mutants…
Autor(en): | Stefan Schäbler, Kelechi M. Amatobi, Melanie Horn, Dirk Rieger, Charlotte Helfrich‑Förster, Martin J. Mueller, Christian Wegener, Agnes Fekete |
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URN: | urn:nbn:de:bvb:20-opus-232432 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Julius-von-Sachs-Institut für Biowissenschaften |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cellular and Molecular Life Sciences |
ISSN: | 1420-682X |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 77 |
Seitenangabe: | 4939–4956 |
Originalveröffentlichung / Quelle: | Cellular and Molecular Life Sciences (2020) 77:4939–4956. https://doi.org/10.1007/s00018-019-03441-6 |
DOI: | https://doi.org/10.1007/s00018-019-03441-6 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Freie Schlagwort(e): | acylcarnitine; circadian rhythms; feeding; metabolomics; mitochondrial activity; tryptophan |
Datum der Freischaltung: | 19.05.2021 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |