Claycombe K J, Jones B H, Standridge M K, Guo Y, Chun J T, Taylor J W, Moustaïd-Moussa N
Department of Nutrition, University of Tennessee, Knoxville 37996-1900, USA.
Am J Physiol. 1998 May;274(5):R1253-9. doi: 10.1152/ajpregu.1998.274.5.R1253.
The purpose of this study was to investigate the molecular mechanism whereby insulin increases expression of a key de novo lipogenic gene, fatty acid synthase (FAS), in cultured human adipocytes and hepatoma cells. RNA isolated from cultured adipocytes or from Hep G2 cells treated with or without insulin (20 nM) was analyzed. In addition, run-on transcription assays and measurements of RNA half-life were performed to determine the controlled step in FAS gene regulation by insulin. We demonstrated that FAS mRNA was expressed in both Hep G2 cells and human adipocytes. Insulin induced an approximately five- and three-fold increase in FAS mRNA content in adipocytes and hepatoma cells, respectively. Similar regulation of FAS was observed in adipocytes from lean and obese human subjects. Furthermore, we demonstrated that the induction of human FAS expression by insulin was due to increased transcription rate of the FAS gene in human adipocytes, whereas mRNA stabilization accounted for increased FAS mRNA content in hepatoma cells. In conclusion, we report here for the first time expression of human FAS mRNA and its specific transcriptional induction by insulin in cultured human adipocytes.
本研究的目的是探究胰岛素在培养的人脂肪细胞和肝癌细胞中增加关键的从头脂肪生成基因脂肪酸合酶(FAS)表达的分子机制。分析了从培养的脂肪细胞或用胰岛素(20 nM)处理或未处理的Hep G2细胞中分离的RNA。此外,进行了连续转录测定和RNA半衰期测量,以确定胰岛素对FAS基因调控的控制步骤。我们证明FAS mRNA在Hep G2细胞和人脂肪细胞中均有表达。胰岛素分别使脂肪细胞和肝癌细胞中的FAS mRNA含量增加约五倍和三倍。在瘦人和肥胖人的脂肪细胞中观察到类似的FAS调控。此外,我们证明胰岛素诱导人FAS表达是由于人脂肪细胞中FAS基因转录速率增加,而mRNA稳定化则导致肝癌细胞中FAS mRNA含量增加。总之,我们首次在此报告人FAS mRNA在培养的人脂肪细胞中的表达及其由胰岛素特异性转录诱导。