脂滴
脂滴(英语:Lipid droplets、Lipid bodies或Adiposomes),[1]是富含脂质的细胞器,可调节中性脂质的储存和水解,主要存在于脂肪组织中。[2]它们还充当胆固醇和甘油酯的储库,用于膜的形成和维持。脂滴存在于所有真核生物中,并在哺乳动物的脂肪细胞中储存了很大一部分脂质。最初,这些脂滴被认为仅作为脂肪库,但自从1990年代在脂滴外壳中发现了调节脂滴动态和脂质代谢的蛋白质后,脂滴被视为高度动态的细胞器,并在调节细胞内脂质储存和脂质代谢方面起着非常重要的作用。脂滴在脂质和胆固醇储存之外的作用渐渐开始被阐明,包括通过类花生酸的合成和代谢与炎症反应以及肥胖、癌症[3][4]和动脉粥样硬化[5]等代谢紊乱的密切关联。在非脂肪细胞中,已知脂滴通过以中性甘油三酯(TAGs)的形式储存脂肪酸,在防止脂肪毒性方面发挥作用,其中甘油三酯由三个与甘油结合的脂肪酸组成。另外,脂肪酸可以转化为脂质中间体,如甘油二酯(DAGs)、神经酰胺和脂酰辅酶A。这些脂质中间体会损害胰岛素信号,这被称为脂质诱导的胰岛素抵抗和脂肪毒性。[6]脂滴也可作为蛋白质结合和降解的平台。最后,已知脂滴会被C型肝炎病毒、骨痛热症病毒和沙眼衣原体等病原体利用。[7][8]
结构
脂滴由中性脂质核心组成,主要由甘油三酯和被磷脂单层包围的胆固醇酯组成。[2]脂滴的表面被一些参与调节脂质代谢的蛋白质所装饰。[2]第一个也是最典型的脂滴外壳蛋白质家族是围脂滴蛋白家族(perilipin protein family),由五种蛋白质组成。这五种蛋白质包括围脂滴蛋白1(PLIN1)、围脂滴蛋白2(PLIN2/ADRP)、[9]围脂滴蛋白3(PLIN3/TIP47)、围脂滴蛋白4(PLIN4/S3-12)和围脂滴蛋白5(PLIN5/OXPAT/LSDP5/MLDP)。[10][11][12]蛋白质组学研究表明了许多其他蛋白质家族与脂质表面的关联,包括参与膜囊泡运输、囊泡对接、胞吞作用和胞吐作用的蛋白质。[13]对脂滴的脂质成分的分析揭示了多种磷脂种类的存在,[14]其中磷脂酰胆碱和磷脂酰乙醇胺的含量最多,其次是磷脂酰肌醇。
脂滴的大小变化很大,从20nm至40nm甚至100um不等。[15]在脂肪细胞中,脂质体往往较大,它们可能构成细胞的大部分,而在其他细胞中,它们可能仅在特定条件下被诱导并且体积小得多。
形成
脂滴从内质网膜上萌芽。最初,晶状体通过在其磷脂双分子层的两层之间积累甘油三酯形成。新生的脂滴可能通过脂肪酸的扩散、甾醇的胞吞作用或借助SNARE蛋白融合较小的脂滴而生长。[15]磷脂的不对称积累促进了脂滴的出芽,并降低了胞质溶胶的表面张力。[16]还观察到脂滴是由现有脂滴裂变产生的,尽管这被认为不如从头形成那么常见。[17]
![](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Lipid_droplets.gif/220px-Lipid_droplets.gif)
内质网中脂滴的形成始于要运输的中性脂质的合成。从甘油二酯制造甘油三酯(通过添加脂肪酰基链)由DGAT蛋白催化,尽管这些蛋白和其他蛋白的需求程度取决于细胞类型。[18]无论是DGAT1或DGAT2都不是甘油三酯合成或液滴形成所必需的,尽管缺乏这两者的哺乳动物细胞不能形成脂滴,并且甘油三酯的合成会严重受阻。DGAT1似乎更喜欢外源性脂肪酸底物,不是生命所必需的;DGAT2似乎更喜欢内源性合成的脂肪酸,是生命所必需的。[17]
在非脂肪细胞中,脂质储存、脂滴合成和脂滴生长可由各种刺激诱导,包括生长因子、长链不饱和脂肪酸(包括油酸和花生四烯酸)、氧化应激和炎症刺激物如细菌脂多糖、各种微生物病原体、血小板活化因子、类花生酸和细胞因子。[19]
一个例子是作为不饱和脂肪酸衍生物的内源性大麻素,它主要被认为是从细胞膜中的磷脂前体“按需要”合成的,但也可能在细胞内脂滴中合成和储存,并在适当条件下从这些储存中释放出来。[20]
使用无标记活细胞成像,可以观察活的和无标记的脂滴的形成。
图像
![Oil bodies in Nardia scalaris, a leafy liverwort](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/c/ce/Nardia_scalaris_Blattzellen_IMG_8353.jpg/200px-Nardia_scalaris_Blattzellen_IMG_8353.jpg)
参见
参考文献
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