A metabolomic strategy defines the regulation of lipid content and global metabolism by Δ9 desaturases in Caenorhabditis elegans.
A metabolomic strategy defines the regulation of lipid content and global metabolism by Δ9 desaturases in Caenorhabditis elegans.
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DOI：
10.1186/1471-2164-13-36
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发表时间：
2012-01-20
期刊：
影响因子：
4.4
通讯作者：
Griffin JL
中科院分区：
文献类型：
--
作者：
Castro C;Sar F;Shaw WR;Mishima M;Miska EA;Griffin JL
秀丽隐杆线虫提供了一种遗传上可处理的模式生物，用于研究参与脂肪代谢的基因网络以及调节如何被扰乱以产生复杂的肥胖表型。秀丽隐杆线虫具有全系列的去饱和酶，包括Δ9由脂肪-5、脂肪-6和脂肪-7表达的去饱和酶。它们调节单不饱和脂肪酸的生物合成，单不饱和脂肪酸用于合成脂类，包括磷脂、甘油三酯和胆固醇酯。使用液相色谱质谱（LC-MS）、气相色谱质谱（GC-MS）和核磁共振（NMR）谱来确定Δ9去饱和酶的所有可能敲除的代谢组，包括首次完整的脂质。尽管这些基因具有相似的酶促作用，但对所有的单突变体和活的双突变体都可以进行很好的区分，突出了脂肪-6和脂肪-7的独特作用，它们都表达甾醇辅酶a去饱和酶。代谢组学变化扩展到水代谢物，表明Δ9去饱和酶对调节整体代谢的影响，并突出了综合代谢组学如何比传统的脂肪染色染料更具歧视性。代谢变化在整个代谢网络中的传播表明，与野生型对照相比，Δ9去饱和酶的修饰使秀丽隐杆线虫进入分解代谢状态。
Caenorhabditis elegans provides a genetically tractable model organism to investigate the network of genes involved in fat metabolism and how regulation is perturbed to produce the complex phenotype of obesity. C. elegans possess the full range of desaturases, including the Δ9 desaturases expressed by fat-5, fat-6 and fat-7. They regulate the biosynthesis of monounsaturated fatty acids, used for the synthesis of lipids including phospholipids, triglycerides and cholesteryl esters. Liquid chromatography mass spectrometry (LC-MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to define the metabolome of all the possible knock-outs for the Δ9 desaturases, including for the first time intact lipids. Despite the genes having similar enzymatic roles, excellent discrimination was achievable for all single and viable double mutants highlighting the distinctive roles of fat-6 and fat-7, both expressing steroyl-CoA desaturases. The metabolomic changes extend to aqueous metabolites demonstrating the influence Δ9 desaturases have on regulating global metabolism and highlighting how comprehensive metabolomics is more discriminatory than classically used dyes for fat staining. The propagation of metabolic changes across the network of metabolism demonstrates that modification of the Δ9 desaturases places C.elegans into a catabolic state compared with wildtype controls.
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影响因子：
3.7
作者：
Brooks KK;Liang B;Watts JL
通讯作者：
Watts JL
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
影响因子：
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作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
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6.5
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9.8
作者：
Kniazeva M;Crawford QT;Seiber M;Wang CY;Han M
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