Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase.

Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase.
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硬脂酰辅酶A去饱和酶调节脂滴大小和磷脂组成

DOI:
10.1194/jlr.m039669
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发表时间:
2013-09
影响因子:
6.5
通讯作者:
Watts JL
Watts JL
中科院分区:
生物学2区
文献类型:
--
作者:
Shi X;Li J;Zou X;Greggain J;Rødkær SV;Færgeman NJ;Liang B;Watts JL

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脂肪酸去饱和调节动物的膜功能和脂肪储存。为了确定硬脂酰辅酶a去饱和酶(SCD)活性对秀丽隐杆线虫脂肪储存和发育的贡献,我们分析了脂肪-6中的脂质组成和脂滴大小;脂肪-7去饱和酶突变体单独或与突变体联合破坏了保守的脂质代谢途径。SCD活性受损的秀丽隐杆线虫显示脂肪储存减少和脂滴大小减小。突变体daf-2(胰岛素样生长因子受体)、risk -1 (p70s6激酶的同源物,雷帕霉素信号通路靶点的效应物)和daf-7(转化生长因子β)显示出高脂肪储存,与fat-6中观察到的低脂肪相反;脂肪-7去饱和酶突变体。代谢突变体与脂肪-6结合;除了daf-2、fat-6和fat-7外,fat-7显示出低脂肪储存。脂肪-7三重突变体,增加了新脂肪酸合成和野生型脂肪储存水平。值得注意的是,在所有突变背景下,SCD活性是形成大尺寸脂滴所必需的,也是磷脂酰胆碱(PC)与磷脂酰乙醇胺(PE)正常比率所必需的。这些研究揭示了SCD在调节脂滴大小和膜磷脂组成中的先前未被描述的作用。
Fatty acid desaturation regulates membrane function and fat storage in animals. To determine the contribution of stearoyl-CoA desaturase (SCD) activity on fat storage and development in the nematode Caenorhabditis elegans, we analyzed the lipid composition and lipid droplet size in the fat-6;fat-7 desaturase mutants independently and in combination with mutants disrupted in conserved lipid metabolic pathways. C. elegans with impaired SCD activity displayed both reduced fat stores and decreased lipid droplet size. Mutants in the daf-2 (insulin-like growth factor receptor), rsks-1 (homolog of p70S6kinase, an effector of the target of rapamycin signaling pathway), and daf-7 (transforming growth factor β) displayed high fat stores, the opposite of the low fat observed in the fat-6;fat-7 desaturase mutants. The metabolic mutants in combination with fat-6;fat-7 displayed low fat stores, with the exception of the daf-2;fat-6;fat-7 triple mutants, which had increased de novo fatty acid synthesis and wild-type levels of fat stores. Notably, SCD activity is required for the formation of large-sized lipid droplets in all mutant backgrounds, as well as for normal ratios of phosphatidylcholine (PC) to phosphatidylethanolamine (PE). These studies reveal previously uncharacterized roles for SCD in the regulation of lipid droplet size and membrane phospholipid composition.