ATF4 regulates SREBP1c expression to control in 3T3-L1 adipocytes differentiation fatty acids synthesis
ATF4 regulates SREBP1c expression to control in 3T3-L1 adipocytes differentiation fatty acids synthesis
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ATF4调节SREBP1c表达以控制3T3-L1脂肪细胞分化脂肪酸合成
DOI：
10.1016/j.bbagrm.2016.07.010
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发表时间：
2016-11-01
影响因子：
4.7
通讯作者：
Chen, Yaosheng
中科院分区：
文献类型：
--
作者：
Chen, Hu;Yuan, Renqiang;Chen, Yaosheng
转录激活因子4（ATF 4）是脂肪细胞分化所必需的，在脂肪诱导后在313-L1脂肪细胞中高度表达。ATF 4在调节脂肪酸生物合成中也起着至关重要的作用，但这一过程的详细机制仍不清楚。在这里，我们证明了3 T3-L1脂肪细胞中基于siRNA的ATF 4消耗显著减少了脂肪酸和甘油三酯的积累。此外，SREBP 1c蛋白，这是一个重要的脂肪生成的转录因子，略有下降，而Srebp 1c mRNA增加。我们进一步证实ATF 4可以通过直接激活USP 7的表达来维持SREBP 1c蛋白的稳定性，USP 7使SREBP 1c去泛素化，增加其在细胞中的蛋白含量。此外，在不存在ATF 4的情况下，USP 7可以恢复脂肪酸和甘油三酯的合成。另一方面，我们发现ATF 4可能通过TRB 3抑制Srebp 1c的转录，TRB 3在早期脂肪形成过程中被IBMX和DEX抑制。因此，我们的数据表明，ATF 4调节SREBP 1c的表达，以控制脂肪酸的合成。(C)2016爱思唯尔B. V.保留所有权利。
Activating transcription factor 4 (ATF4), which is highly expressed in 313-L1 adipocytes after adipogenic induction, is essential for adipocytes differentiation. ATF4 also plays a vital role in regulating fatty acids biosynthesis, whereas the detailed mechanism of this process is still unclear. Here we demonstrated that siRNA-based ATF4 depletion in 3T3-L1 adipocytes significantly reduced the accumulation of fatty acids and triglycerides. Moreover, SREBP1c protein, which is an important transcription factor of lipogenesis, appreciably decreased while Srebp1c mRNA increased. Then we identified that ATF4 could maintain SREBP1c protein stability by directly activating the expression of USP7 which deubiquitinates SREBP1c and increases its protein content in cell. Besides, USP7 could restore the synthesis of fatty acids and triglycerides in the absence of ATF4. On the other hand, we found that ATF4 might inhibit the transcription of Srebp1c through TRB3, which is repressed by IBMX and DEX during early adipogenesis. Thus, our data indicate that ATF4 regulates SREBP1c expression to control fatty acids synthesis. (C) 2016 Elsevier B.V. All rights reserved.