Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis
Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis
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DOI：
10.1073/pnas.0502383102
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发表时间：
2005-08-23
影响因子：
11.1
通讯作者：
Tezuka, M
中科院分区：
文献类型：
--
作者：
Shimba, S;Ishii, N;Tezuka, M
脑和肌肉Arnt样蛋白-1（BMAL 1;也称为MOP 3或Arnt 3）是已知调节昼夜节律的转录因子。在这里，我们确定了它参与控制成熟脂肪细胞的脂肪生成和脂质代谢活性。在3 T3-L1细胞的脂肪分化过程中，BMAL 1 mRNA的水平在诱导后4天开始增加，并且在分化的细胞中高度表达。在从C57 BL/6 J小鼠分离的白色脂肪组织中，与基质-血管组分相比，BMAL 1主要在含有脂肪细胞的组分中表达。BMAL 1基因敲除小鼠胚胎成纤维细胞未能分化为脂肪细胞。重要的是，通过腺病毒基因转移将BMAL 1重新加入，恢复了BMAL 1敲除小鼠胚胎成纤维细胞的分化能力。通过RNA干扰技术敲低3 T3-L1细胞中的BMAL 1表达允许细胞在细胞中仅积累最少量的脂滴。腺病毒介导的BMAL 1在3 T3-L1脂肪细胞中的表达导致了参与脂肪生成的几种因子的诱导。这些基因的启动子活性以BMAL 1依赖的方式被刺激。有趣的是，这些因子的表达在小鼠脂肪组织中显示出明显的昼夜节律。此外，BMAL 1在脂肪细胞中的过表达增加了脂质合成活性。这些结果表明，BMAL 1，昼夜节律的主调节器，在成熟脂肪细胞的脂肪分化和脂肪生成的调节中也起着重要作用。
Brain and muscle Arnt-like protein-1 (BMAL1; also known as MOP3 or Arnt3) is a transcription factor known to regulate circadian rhythm. Here, we established its involvement in the control of adipogenesis and lipid metabolism activity in mature adipocytes. During adipose differentiation in 3T3-L1 cells, the level of BMAL1 mRNA began to increase 4 days after induction and was highly expressed in differentiated cells. In white adipose tissues isolated from C57BL/6J mice, BMAL1 was predominantly expressed in a fraction containing adipocytes, as compared with the stromal-vascular fraction. BMAL1 knockout mice embryonic fibroblast cells failed to be differentiated into adipocytes. Importantly, adding BMAL1 back by adenovirus gene transfer restored the ability of BMAL1 knockout mice embryonic fibroblast cells to differentiate. Knock-down of BMAL1 expression in 3T3-L1 cells by an RNA interference technique allowed the cells to accumulate only minimum amounts of lipid droplets in the cells. Adenovirus-mediated expression of BMAL1 in 3T3-L1 adipocytes resulted in induction of several factors involved in lipogenesis. The promoter activity of these genes was stimulated in a BMAL1-dependent manner. Interestingly, expression of these factors showed clear circadian rhythm in mice adipose tissue. Furthermore, overexpression of BMAL1 in adipocytes increased lipid synthesis activity. These results indicate that BMAL1, a master regulator of circadian rhythm, also plays important roles in the regulation of adipose differentiation and lipogenesis in mature adipocytes.