Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase
Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase
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DOI：
10.1074/jbc.c114.563080
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发表时间：
2014-05-23
影响因子：
4.8
通讯作者：
Kandror, Konstantin V.
中科院分区：
文献类型：
--
作者：
Singh, Maneet;Kaur, Rajween;Kandror, Konstantin V.
脂肪组织中的脂解是循环脂肪酸的主要来源。先前，我们已经发现脂肪细胞中的脂解由早期生长反应转录因子Egr 1控制，Egr 1直接抑制脂肪甘油三酯脂肪酶ATGL的转录（Chakrabarti，P.，金，J.Y.，辛格，M.，申，Y。K.，金，J.，Kumbrink，J.，吴，Y.，李，M。J.，Kirsch，K. H、弗里德，S。K.，和Kandror，K. V.（2013）Mol. Cell. 33，3659-3666）。在这里，我们证明了脂滴蛋白FSP 27（a.k.a. CIDEC）在人脂肪细胞中在转录水平上增加ATGL的表达，而FSP 27的过表达具有相反的作用。FSP 27在体外抑制ATGL启动子的活性，并且近端Egr 1结合位点负责这种效应。FSP 27与Egr 1共免疫沉淀，并增加其与ATGL启动子的结合和抑制。Egr 1的敲低减弱了FSP 27的抑制作用。这些结果为ATGL的转录调控提供了一个新的模型。
Lipolysis in fat tissue represents a major source of circulating fatty acids. Previously, we have found that lipolysis in adipocytes is controlled by early growth response transcription factor Egr1 that directly inhibits transcription of adipose triglyceride lipase, ATGL (Chakrabarti, P., Kim, J. Y., Singh, M., Shin, Y. K., Kim, J., Kumbrink, J., Wu, Y., Lee, M. J., Kirsch, K. H., Fried, S. K., and Kandror, K. V. (2013) Mol. Cell. Biol. 33, 3659-3666). Here we demonstrate that knockdown of the lipid droplet protein FSP27 (a.k.a. CIDEC) in human adipocytes increases expression of ATGL at the level of transcription, whereas overexpression of FSP27 has the opposite effect. FSP27 suppresses the activity of the ATGL promoter in vitro, and the proximal Egr1 binding site is responsible for this effect. FSP27 co-immunoprecipitates with Egr1 and increases its association with and inhibition of the ATGL promoter. Knockdown of Egr1 attenuates the inhibitory effect of FSP27. These results provide a new model of transcriptional regulation of ATGL.