The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans.
The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans.
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DOI：
10.1371/journal.pone.0009869
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发表时间：
2010-03-25
期刊：
影响因子：
3.7
通讯作者：
Watts JL
中科院分区：
文献类型：
--
作者：
Liang B;Ferguson K;Kadyk L;Watts JL
核激素受体（NHRs）在调节代谢、生殖和发育中起着重要作用。我们发现C.线虫HNF 4同源物nhr-64通过RNA干扰（RNAi）抑制硬脂酰辅酶A去饱和酶缺陷型fat-6;fat-7双突变体和固醇调节元件结合蛋白（SREBP）sbp-1突变体中的低脂肪储存。此外，nhr-64的失活提高了fat-6、fat-7和sbp-1菌株的生长速率。而nhr-64 RNAi则微妙地影响野生型C.在线虫中，其对脂质代谢的影响在硬脂酰辅酶A去饱和酶或SREBP缺乏的背景下最明显。当在酵母中表达时，NHR-64显示转录激活活性，并且nhr-64的失活影响至少14个代谢基因的表达。用nhr-64 RNAi处理的野生型蠕虫显示乙酰辅酶A羧化酶的表达增加以及从头合成的单甲基支链脂肪酸的丰度增加，表明脂肪合成增加。然而，乙酰辅酶A合成酶基因acs-2和酰基辅酶A氧化酶基因的表达减少表明NHR-64的关键作用可能是促进线粒体和过氧化物酶体中的脂肪酸氧化。这些研究表明NHR-64是C.优雅
Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and sterol regulatory element binding protein (SREBP) sbp-1 mutants. Furthermore, inactivation of nhr-64 improves the growth rate of the fat-6;fat-7and sbp-1 strains. While nhr-64RNAi subtly affects fatty acid composition and fat storage in wild-type C. elegans, its effects on lipid metabolism are most apparent in the background of stearoyl-CoA desaturase or SREBP deficiency. NHR-64 displays transcriptional activating activity when expressed in yeast, and inactivation of nhr-64 affects the expression of at least 14 metabolic genes. Wild-type worms treated with nhr-64 RNAi display increased expression of acetyl-CoA carboxylase as well as increased abundance of de novo synthesized monomethyl branched chain fatty acids, suggesting an increase in fat synthesis. However, reduced expression of the acetyl-CoA synthetase gene acs-2 and an acyl-CoA oxidase gene indicates that a key role of NHR-64 may be to promote fatty acid oxidation in mitochondria and peroxisomes. These studies reveal that NHR-64 is an important regulator of fat storage in C. elegans.
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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：
4.5
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
通讯作者：
Watts, Jennifer L.
影响因子：
4.8
作者：
Dhe-Paganon, S;Duda, K;Shoelson, SE
通讯作者：
Shoelson, SE
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
影响因子：
29
作者：
Perez, Carissa L.;Van Gilst, Marc R.
通讯作者：
Van Gilst, Marc R.