Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation.
Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation.
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DOI：
10.1007/s00018-019-03441-6
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Fekete A
中科院分区：
文献类型：
--
作者：
Schäbler S;Amatobi KM;Horn M;Rieger D;Helfrich-Förster C;Mueller MJ;Wegener C;Fekete A
果蝇是昼夜节律研究的主要模型，但对其代谢的昼夜节律调节知之甚少。已经发现了几种代谢物水平的每日节律性，但关于疏水代谢物的知识有限。我们在这里比较代谢物水平，包括周期01（per 01）时钟突变体和广州-S野生型（WTCS）苍蝇在同基因和非同基因背景下使用LC-MS之间的脂质。在非等基因背景下，具有不同水平的代谢物包括必需氨基酸、犬尿氨酸、蝶呤、甘油（磷酸）脂质和脂肪酸酯。值得注意的是，可检测的二酰基甘油（DAG）和酰基肉毒碱（AC），参与脂质代谢，表现出较低的水平在per 01突变体。大多数这些差异消失在同基因背景，但AC以及DAG的水平差异是一致的苍蝇机构。AC水平依赖于一天中的时间在WTCS与LD条件下的食物消耗的阶段，而DAGs表现出较弱的每日振荡。两个短链AC即使在持续的黑暗中也继续循环。LD中的per 01突变体显示没有或非常弱的与摄食活性异相的昼夜AC振荡。per 01中的低水平的DAG和AC与较低的总食物消耗量、体重或体重无关。时钟突变苍蝇表现出更高的敏感性饥饿独立的背景依赖的活动水平。我们的研究结果表明，无论是进食，能量储存，也不动员是显着影响per 01突变体，但指向受损的线粒体活性，支持上调的线粒体应激标记4 EBP的时钟突变体。本文的在线版本（10.1007/s 00018 -019-03441-6）包含补充材料，可供授权用户使用。
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. The online version of this article (10.1007/s00018-019-03441-6) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S
影响因子：
3.5
作者：
Hughes ME;Hogenesch JB;Kornacker K
通讯作者：
Kornacker K
影响因子：
3.7
作者：
DiAngelo, Justin R.;Erion, Renske;Sehgal, Amita
通讯作者：
Sehgal, Amita
DOI：
10.1016/j.biocel.2003.11.016
发表时间：
2004-11-01
影响因子：
4
作者：
Avila, MA;García-Trevijano, ER;Mato, JM
通讯作者：
Mato, JM