The ARF-Like GTPase ARFRP1 Is Essential for Lipid Droplet Growth and Is Involved in the Regulation of Lipolysis
The ARF-Like GTPase ARFRP1 Is Essential for Lipid Droplet Growth and Is Involved in the Regulation of Lipolysis
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DOI：
10.1128/mcb.01269-09
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发表时间：
2010-03-01
影响因子：
5.3
通讯作者：
Schuermann, Annette
中科院分区：
文献类型：
--
作者：
Hommel, Angela;Hesse, Deike;Schuermann, Annette
ADP核糖基化因子相关蛋白1（ARFRP 1）是一种调节细胞内细胞器之间蛋白运输的GTP酶。在这里，我们表明脂肪细胞中缺乏Arfrp 1的小鼠（Arfrp 1（ad-/-））由于脂肪细胞中脂滴形成缺陷而出现脂肪营养不良。甘油单酯、甘油二酯和甘油三酯的比例以及甘油三酯的脂肪酸组成均未改变。ARFRP 1（ad-/-）小鼠棕色脂肪细胞的脂滴相当小，并表现出超微结构的改变，如小的脂质负载颗粒与较大的液滴的干扰相互作用，这表明ARFRP 1介导新形成的小脂质颗粒转移到大的存储液滴。SNAP 23（23 kDa的突触体相关蛋白）与对照脂肪细胞的小脂滴相关，但主要位于Arfrp 1（ad-/-）脂肪细胞的胞质溶胶中，表明Arfrp 1（ad-/-）小鼠的脂滴生长有缺陷。此外，在Arfrp 1（ad-/-）小鼠的棕色脂肪组织中，磷酸化脂肪酸敏感脂肪酶（HSL）水平升高，脂肪细胞甘油三酯脂肪酶（ATGL）与脂滴的结合增强。因此，在3 T3-L1脂肪细胞中敲低Arfrp 1后，基础脂解增加。这些数据表明，ARFRP 1的破坏阻止了脂滴的正常扩大，并产生了脂解的激活。
ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a GTPase regulating protein trafficking between intracellular organelles. Here we show that mice lacking Arfrp1 in adipocytes (Arfrp1(ad-/-)) are lipodystrophic due to a defective lipid droplet formation in adipose cells. Ratios of mono-, di-, and triacylglycerol, as well as the fatty acid composition of triglycerides, were unaltered. Lipid droplets of brown adipocytes of Arfrp1(ad-/-) mice were considerably smaller and exhibited ultrastructural alterations, such as a disturbed interaction of small lipid-loaded particles with the larger droplets, suggesting that ARFRP1 mediates the transfer of newly formed small lipid particles to the large storage droplets. SNAP23 (synaptosomal-associated protein of 23 kDa) associated with small lipid droplets of control adipocytes but was located predominantly in the cytosol of Arfrp1(ad-/-) adipocytes, suggesting that lipid droplet growth is defective in Arfrp1(ad-/-) mice. In addition, levels of phosphorylated hormone-sensitive lipase (HSL) were elevated, and association of adipocyte triglyceride lipase (ATGL) with lipid droplets was enhanced in brown adipose tissue from Arfrp1(ad-/-) mice. Accordingly, basal lipolysis was increased after knockdown of Arfrp1 in 3T3-L1 adipocytes. The data indicate that disruption of ARFRP1 prevents the normal enlargement of lipid droplets and produces an activation of lipolysis.