TY  - JOUR
A1  - Schäbler, Stefan
A1  - Amatobi, Kelechi M.
A1  - Horn, Melanie
A1  - Rieger, Dirk
A1  - Helfrich‑Förster, Charlotte
A1  - Mueller, Martin J.
A1  - Wegener, Christian
A1  - Fekete, Agnes
T1  - Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation
JF  - Cellular and Molecular Life Sciences
N2  - 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 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
KW  - circadian rhythms
KW  - metabolomics
KW  - mitochondrial activity
KW  - tryptophan
KW  - acylcarnitine
KW  - feeding
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232432
SN  - 1420-682X
VL  - 77
ER  -