Genetic regulation of unsaturated fatty acid composition in C. elegans.
Genetic regulation of unsaturated fatty acid composition in C. elegans.
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秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
DOI：
10.1371/journal.pgen.0020108
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发表时间：
2006-07
期刊：
影响因子：
4.5
通讯作者：
Watts, Jennifer L.
中科院分区：
文献类型：
--
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
Δ-9去饱和酶，也称为硬脂酰辅酶A去饱和酶，是负责产生膜和能量储存分子的重要组分的脂肪生成酶。我们已经确定了一种新的核激素受体，NHR-80，调节δ-9去饱和酶基因表达的秀丽隐杆线虫。在这里，我们描述了携带nhr-80突变和编码delta-9去饱和酶fat-5、fat-6和fat-7的三个基因突变的菌株的脂肪酸组成、寿命和基因表达研究。δ-9去饱和酶单突变体仅显示脂肪酸组成的细微变化，没有其他可见的表型，而fat-5;fat-6;fat-7三重突变体是致命的，揭示了内源性单不饱和脂肪酸的产生对于生存是必不可少的。在不存在FAT-6或FAT-7的情况下，剩余去饱和酶的表达增加，并且这种补偿能力取决于NHR-80。我们的结论是，像哺乳动物一样，C。线虫需要充分合成不饱和脂肪酸并维持δ-9去饱和酶的复杂调节以获得最佳脂肪酸组成。饱和脂肪酸与不饱和脂肪酸的比例对细胞膜的流动性和功能有着深远的影响。动物、植物和微生物在不断变化的环境条件下调节不饱和脂肪酸的合成，以及对膳食营养素的反应。在本文中，作者使用遗传学和生物化学方法相结合，以解决不饱和脂肪酸的合成在蛔虫秀丽隐杆线虫的调节。他们确定了一种新的转录因子NHR-80，它激活了编码delta-9脂肪酸去饱和酶的基因的表达，这种酶负责催化双键插入饱和脂肪酸链。这些不饱和脂肪酸是膜的关键组成部分，也是脂肪储存分子。这里提出的实验表明，蠕虫需要足够的不饱和脂肪酸的合成生存，他们保持复杂的三个三角洲-9去饱和酶基因的调节，以应对不同的营养物质。脂质代谢异常导致人类肥胖和糖尿病，这项研究有助于我们了解这一代谢途径的调控。
Delta-9 desaturases, also known as stearoyl-CoA desaturases, are lipogenic enzymes responsible for the generation of vital components of membranes and energy storage molecules. We have identified a novel nuclear hormone receptor, NHR-80, that regulates delta-9 desaturase gene expression in Caenorhabditis elegans. Here we describe fatty acid compositions, lifespans, and gene expression studies of strains carrying mutations in nhr-80 and in the three genes encoding delta-9 desaturases, fat-5, fat-6, and fat-7. The delta-9 desaturase single mutants display only subtle changes in fatty acid composition and no other visible phenotypes, yet the fat-5;fat-6;fat-7 triple mutant is lethal, revealing that endogenous production of monounsaturated fatty acids is essential for survival. In the absence of FAT-6 or FAT-7, the expression of the remaining desaturases increases, and this ability to compensate depends on NHR-80. We conclude that, like mammals, C. elegans requires adequate synthesis of unsaturated fatty acids and maintains complex regulation of the delta-9 desaturases to achieve optimal fatty acid composition. The ratio of saturated to unsaturated fatty acids has a profound affect on the fluidity and function of cellular membranes. Animals, plants, and microorganisms regulate the synthesis of unsaturated fatty acids during changing environmental conditions, as well as in response to dietary nutrients. In this paper the authors use a combination of genetic and biochemical approaches to address the regulation of unsaturated fatty acid synthesis in the roundworm Caenorhabditis elegans. They identify a new transcription factor, NHR-80, that activates the expression of genes encoding delta-9 fatty acid desaturases, the enzymes responsible for catalyzing the insertion of double bonds into saturated fatty acid chains. These unsaturated fatty acids are critical components of membranes, as well as fat storage molecules. Experiments presented here demonstrate that the worms require adequate synthesis of unsaturated fatty acids for survival and that they maintain intricate regulation of the three delta-9 desaturase genes in response to different nutrients. Abnormalities in lipid metabolism lead to obesity and diabetes in humans; this study contributes to our understanding of the regulation of this metabolic pathway.
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影响因子：
2.7
作者：
Miyabayashi, T;Palfreyman, MT;Sengupta, P
通讯作者：
Sengupta, P
影响因子：
3.9
作者：
Robinson-Rechavi, M;Maina, CV;Sluder, A
通讯作者：
Sluder, A
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
1.9
作者：
Ntambi, JM;Miyazaki, A;Dobrzyn, A
通讯作者：
Dobrzyn, A
DOI：
10.1073/pnas.132384699
发表时间：
2002-08-20
影响因子：
11.1
作者：
Ntambi, JM;Miyazaki, M;Attie, AD
通讯作者：
Attie, AD