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Publication : ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation.

First Author  Chen H Year  2016
Journal  Biochim Biophys Acta Volume  1859
Issue  11 Pages  1459-1469
PubMed ID  27452504 Mgi Jnum  J:250926
Mgi Id  MGI:6106217 Doi  10.1016/j.bbagrm.2016.07.010
Citation  Chen H, et al. (2016) ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation. Biochim Biophys Acta 1859(11):1459-1469
abstractText  Activating transcription factor 4 (ATF4), which is highly expressed in 3T3-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.
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