Dicer has a crucial role in the early stage of adipocyte differentiation, but not in lipid synthesis, in 3T3-L1 cells
Dicer has a crucial role in the early stage of adipocyte differentiation, but not in lipid synthesis, in 3T3-L1 cells
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DOI：
10.1016/j.bbrc.2012.03.110
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发表时间：
2012-04-20
影响因子：
3.1
通讯作者：
Shimano, Hitoshi
中科院分区：
文献类型：
--
作者：
Fujimoto, Yuri;Nakagawa, Yoshimi;Shimano, Hitoshi
迪格尔是合成微核糖核酸(MiRNA)的限速酶。为了确定DICER在脂肪形成中的作用，我们在3T3-L1细胞中利用编码短发夹状RNAi的腺病毒对DICER进行了阶段特异性的敲除。在3T3-L1细胞分化过程中，腺病毒感染后脂肪细胞分化诱导因子PPAR-γ、C/EBPα和Fas的基因表达受到抑制。同时，与对照RNAi相比，DICER RNAi抑制了脂肪细胞的分化和细胞内脂肪的积累。同时，我们讨论了在分化的最后阶段，DICER在脂肪合成和积累中的作用。将诱导分化后第4天的分化细胞用腺病毒Disher RNAi感染后，细胞内脂质堆积无明显变化。与此一致的是，DICER RNAi对细胞脂质积累相关基因的表达没有影响，包括PPARγ和Fas。因此，DICER通过调节miRNA的合成，在脂肪形成的早期而不是晚期控制成脂基因，如C/EBPα和PPARγ。(C)2012 Elsevier Inc.保留所有权利。
Dicer is a rate-limiting enzyme for microRNA (miRNA) synthesis. To determine the effects of Dicer on adipogenesis, we performed stage-specific knockdown of Dicer using adenovirus encoding short-hairpin RNAi against Dicer in 3T3-L1 cells. When cells were infected with the adenovirus before induction of adipocyte differentiation, Dicer RNAi suppressed the gene expression of inducers of adipocyte differentiation such as PPAR gamma, C/EBP alpha, and FAS in 3T3-L1 cells during adipocyte differentiation. Concurrently, both adipocyte differentiation and cellular lipid accumulation were cancelled by Dicer RNAi when compared with control RNAi. Meanwhile, we addressed the roles of Dicer in lipid synthesis and accumulation in the final stages of differentiation. When the differentiated cells at day 4 after induction of differentiation were infected with adenovirus Dicer RNAi, cellular lipid accumulation was unchanged. Consistent with this, Dicer RNAi had no effects on the expression of genes related to cellular lipid accumulation, including PPAR gamma and FAS. Thus, Dicer controls proadipogenic genes such as C/EBP alpha and PPAR gamma in the early, but not in the late, stage of adipogenesis via regulation of miRNA synthesis. (C) 2012 Elsevier Inc. All rights reserved.