脂滴
脂滴(英語:Lipid droplets、Lipid bodies或Adiposomes),[1]是富含脂質的細胞器,可調節中性脂質的儲存和水解,主要存在於脂肪組織中。[2]它們還充當膽固醇和甘油酯的儲庫,用於膜的形成和維持。脂滴存在於所有真核生物中,並在哺乳動物的脂肪細胞中儲存了很大一部分脂質。最初,這些脂滴被認為僅作為脂肪庫,但自從1990年代在脂滴外殼中發現了調節脂滴動態和脂質代謝的蛋白質後,脂滴被視為高度動態的細胞器,並在調節細胞內脂質儲存和脂質代謝方面起着非常重要的作用。脂滴在脂質和膽固醇儲存之外的作用漸漸開始被闡明,包括通過類花生酸的合成和代謝與炎症反應以及肥胖、癌症[3][4]和動脈粥樣硬化[5]等代謝紊亂的密切關聯。在非脂肪細胞中,已知脂滴通過以中性三酸甘油酯(TAGs)的形式儲存脂肪酸,在防止脂肪毒性方面發揮作用,其中三酸甘油酯由三個與甘油結合的脂肪酸組成。另外,脂肪酸可以轉化為脂質中間體,如甘油二酯(DAGs)、神經酰胺和脂酰輔酶A。這些脂質中間體會損害胰島素信號,這被稱為脂質誘導的胰島素抵抗和脂肪毒性。[6]脂滴也可作為蛋白質結合和降解的平台。最後,已知脂滴會被丙型肝炎病毒、登革熱病毒和沙眼衣原體等病原體利用。[7][8]
結構
脂滴由中性脂質核心組成,主要由三酸甘油酯和被磷脂單層包圍的膽固醇酯組成。[2]脂滴的表面被一些參與調節脂質代謝的蛋白質所裝飾。[2]第一個也是最典型的脂滴外殼蛋白質家族是圍脂滴蛋白家族(perilipin protein family),由五種蛋白質組成。這五種蛋白質包括圍脂滴蛋白1(PLIN1)、圍脂滴蛋白2(PLIN2/ADRP)、[9]圍脂滴蛋白3(PLIN3/TIP47)、圍脂滴蛋白4(PLIN4/S3-12)和圍脂滴蛋白5(PLIN5/OXPAT/LSDP5/MLDP)。[10][11][12]蛋白質組學研究表明了許多其他蛋白質家族與脂質表面的關聯,包括參與膜囊泡運輸、囊泡對接、胞吞作用和胞吐作用的蛋白質。[13]對脂滴的脂質成分的分析揭示了多種磷脂種類的存在,[14]其中磷脂酰膽鹼和磷脂酰乙醇胺的含量最多,其次是磷脂酰肌醇。
脂滴的大小變化很大,從20nm至40nm甚至100um不等。[15]在脂肪細胞中,脂質體往往較大,它們可能構成細胞的大部分,而在其他細胞中,它們可能僅在特定條件下被誘導並且體積小得多。
形成
脂滴從內質網膜上萌芽。最初,晶狀體通過在其磷脂雙分子層的兩層之間積累三酸甘油酯形成。新生的脂滴可能通過脂肪酸的擴散、甾醇的胞吞作用或藉助SNARE蛋白融合較小的脂滴而生長。[15]磷脂的不對稱積累促進了脂滴的出芽,並降低了胞質溶膠的表面張力。[16]還觀察到脂滴是由現有脂滴裂變產生的,儘管這被認為不如從頭形成那麼常見。[17]
![](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Lipid_droplets.gif/220px-Lipid_droplets.gif)
內質網中脂滴的形成始於要運輸的中性脂質的合成。從甘油二酯製造三酸甘油酯(通過添加脂肪酰基鏈)由DGAT蛋白催化,儘管這些蛋白和其他蛋白的需求程度取決於細胞類型。[18]無論是DGAT1或DGAT2都不是三酸甘油酯合成或液滴形成所必需的,儘管缺乏這兩者的哺乳動物細胞不能形成脂滴,並且三酸甘油酯的合成會嚴重受阻。DGAT1似乎更喜歡外源性脂肪酸底物,不是生命所必需的;DGAT2似乎更喜歡內源性合成的脂肪酸,是生命所必需的。[17]
在非脂肪細胞中,脂質儲存、脂滴合成和脂滴生長可由各種刺激誘導,包括生長因子、長鏈不飽和脂肪酸(包括油酸和花生四烯酸)、氧化應激和炎症刺激物如細菌脂多糖、各種微生物病原體、血小板活化因子、類花生酸和細胞因子。[19]
一個例子是作為不飽和脂肪酸衍生物的內源性大麻素,它主要被認為是從細胞膜中的磷脂前體「按需要」合成的,但也可能在細胞內脂滴中合成和儲存,並在適當條件下從這些儲存中釋放出來。[20]
使用無標記活細胞成像,可以觀察活的和無標記的脂滴的形成。
圖像
![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)
參見
參考文獻
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