The regulation of fatty acid synthase by STAT5A
The regulation of fatty acid synthase by STAT5A
复制标题
DOI：
10.2337/diabetes.54.7.1968
复制
发表时间：
2005-07-01
期刊：
影响因子：
7.7
通讯作者：
Stephens, JM
中科院分区：
文献类型：
--
作者：
Hogan, JC;Stephens, JM
生长激素（GH）减少体内脂肪组织质量，并降低脂肪细胞中脂肪酸合成酶（FAS）的表达和活性。GH和催乳素（PRL）是STAT 5的有效激活剂，在脂肪细胞中发挥成脂和抗成脂作用。在这项研究中，我们证明，生长激素和催乳素降低FAS在3 T3-L1脂肪细胞的mRNA和蛋白水平。我们目前的证据表明，FAS是在转录水平上受到抑制。此外，PRL反应性显示存在于大鼠FAS启动子的-1，594和-700之间。此外，对PRL的反应性随着位置-908至-893处的位点的突变而消除，我们已经证明该位点以PRL依赖性方式结合STAT 5A。总而言之，这些数据强烈表明PRL通过STAT 5A结合到-908至-893位点直接抑制脂肪细胞中FAS的表达。此外，我们的研究结果表明，STAT 5A在脂肪细胞中具有抗脂肪生成功能，并可能有助于调节能量平衡。
Growth hormone (GH) diminishes adipose tissue mass in vivo and decreases expression and activity of fatty acid synthase (FAS) in adipocytes. GH and prolactin (PRL) are potent activators of STAT5 and exert adipogenic and antiadipogenic effects in adipocytes. In this study, we demonstrate that GH and PRL decrease the mRNA and protein levels of FAS in 3T3-L1 adipocytes. We present evidence that indicates that FAS is repressed at the level of transcription. In addition, PRL responsiveness was shown to exist between -1,594 and -700 of the rat FAS promoter. Moreover, responsiveness to PRL was abolished with mutation of a site at position -908 to -893, which we have shown to bind STAT5A in a PRL-dependent manner. Taken together, these data strongly suggest that PRL directly represses expression of FAS in adipocytes through STAT5A binding to the -908 to -893 site. Furthermore, our results indicate that STAT5A has an antilipogenic function in adipocytes and may contribute to the regulation of energy balance.