Cell death-inducing DFF45-like effector, a lipid droplet-associated protein, might be involved in the differentiation of human adipocytes
Cell death-inducing DFF45-like effector, a lipid droplet-associated protein, might be involved in the differentiation of human adipocytes
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诱导细胞死亡的 DFF45 样效应蛋白是一种脂滴相关蛋白，可能参与人类脂肪细胞的分化
DOI：
10.1111/j.1742-4658.2010.07806.x
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发表时间：
2010-10-01
期刊：
影响因子：
5.4
通讯作者：
Li, Qing
中科院分区：
文献类型：
--
作者：
Li, Fanfan;Gu, Yu;Li, Qing
细胞死亡诱导DFF45样效应器(CIDE)家族蛋白包括细胞死亡诱导DFF45样效应器A(CIDEA)、细胞死亡诱导DFF45样效应器B(CIDEB)和细胞死亡诱导DFF45样效应器C(CIDEC)[啮齿类动物27 kDa脂肪特异性蛋白(FSP27)]，最初是通过它们与DNA片段因子DFF40/45 N端序列的同源性来鉴定的。最近的研究表明，CIDE家族蛋白在脂质代谢中起着重要作用。几项涉及基因敲除小鼠的研究表明，FSP27是一种脂滴靶向蛋白，可以促进脂滴的形成。然而，人类CIDEC在人类脂肪细胞分化中的具体作用仍不清楚。在本研究中，我们发现CIDEC在胎儿脂肪组织分化过程中表达增加，而在脂肪细胞肿瘤去分化过程中表达降低，提示CIDEC的表达与脂肪细胞的分化呈正相关。此外，我们还证实了人CIDEC定位于脂滴表面。利用人原代前脂肪细胞，我们证实了CIDEC在前脂肪细胞分化过程中的表达上调，而CIDEC在人原代前脂肪细胞中的表达下调导致分化缺陷。这些数据表明，CIDEC对脂肪组织的分化是必不可少的。CIDEC与调节脂肪细胞脂代谢一样，有望成为调节脂肪细胞分化和减少脂肪细胞质量的潜在靶点。
Cell death-inducing DFF45-like effector (CIDE) family proteins, including cell death-inducing DFF45-like effector A (CIDEA), cell death-inducing DFF45-like effector B (CIDEB) and cell death-inducing DFF45-like effector C (CIDEC) [fat-specific protein of 27 kDa in rodent (FSP27) in rodents], were originally identified by their sequence homology to the N-terminal region of DNA fragmentation factor DFF40/45. Recent reports have revealed that CIDE family proteins play important roles in lipid metabolism. Several studies involving knockdown mice revealed that FSP27 is a lipid droplet-targeting protein that can promote the formation of lipid droplets. However, the detailed roles of human CIDEC in the differentiation of human adipocytes remain unknown. In the present study, we found that the expression of CIDEC increased during the differentiation of fetal adipose tissues, but decreased during the de-differentiation of adipocytic tumors, suggesting that the expression of CIDEC should be positively correlated with the differentiation of adipocytes. Furthermore, we verified that human CIDEC was localized on the surface of lipid droplets. Using human primary pre-adipocytes, we confirmed that the expression of CIDEC was elevated during the differentiation of pre-adipocytes, and knockdown of CIDEC in human primary pre-adipocytes resulted in differentiation defects. These data demonstrate that CIDEC is essential for the differentiation of adipose tissue. Together with regulating adipocyte lipid metabolism, CIDEC should be a potential target for regulating adipocyte differentiation and reducing fat cell mass.