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细胞凋亡诱导因子 DFF45 样效应物,一种与脂滴相关的蛋白,可能参与了人脂肪细胞的分化。

Cell death-inducing DFF45-like effector, a lipid droplet-associated protein, might be involved in the differentiation of human adipocytes.

机构信息

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, China.

出版信息

FEBS J. 2010 Oct;277(20):4173-83. doi: 10.1111/j.1742-4658.2010.07806.x.

Abstract

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.

摘要

细胞凋亡诱导因子 DFF45 样效应蛋白(CIDE)家族蛋白,包括细胞凋亡诱导因子 DFF45 样效应蛋白 A(CIDEA)、细胞凋亡诱导因子 DFF45 样效应蛋白 B(CIDEB)和细胞凋亡诱导因子 DFF45 样效应蛋白 C(CIDEC)[啮齿动物中的脂肪特异性蛋白 27 kDa(FSP27)],最初是通过其与 DNA 片段化因子 DFF40/45 的 N 端区域的序列同源性来鉴定的。最近的报道表明,CIDE 家族蛋白在脂质代谢中发挥重要作用。涉及敲低小鼠的几项研究表明,FSP27 是一种脂质滴靶向蛋白,可促进脂质滴的形成。然而,人类 CIDEC 在人脂肪细胞分化中的详细作用仍不清楚。在本研究中,我们发现 CIDEC 的表达在胎儿脂肪组织的分化过程中增加,但在脂肪瘤的去分化过程中减少,这表明 CIDEC 的表达应与脂肪细胞的分化呈正相关。此外,我们验证了人类 CIDEC 定位于脂质滴的表面。使用人原代前体脂肪细胞,我们证实了 CIDEC 的表达在前体脂肪细胞分化过程中升高,并且人原代前体脂肪细胞中 CIDEC 的敲低导致分化缺陷。这些数据表明 CIDEC 对于脂肪组织的分化是必需的。除了调节脂肪细胞的脂质代谢外,CIDEC 还应该是调节脂肪细胞分化和减少脂肪细胞数量的潜在靶点。

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