Compensatory increase in lipogenic gene expression in adipose tissue of transgenic mice expressing constitutively active AMP-activated protein kinase-alphal in liver
Compensatory increase in lipogenic gene expression in adipose tissue of transgenic mice expressing constitutively active AMP-activated protein kinase-alphal in liver
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DOI：
10.1016/j.bbrc.2011.07.078
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发表时间：
2011-08-26
影响因子：
3.1
通讯作者：
Yang, Jian
中科院分区：
文献类型：
--
作者：
Knowles, Christi;Liu, Zhi-Mei;Yang, Jian
我们先前描述了一种在具有肝脏控制区序列的肝脏特异性人apoE启动子控制下选择性表达组成型活性AMPK-α 1的转基因小鼠。在短期激活中，由于胆固醇和脂肪酸合成途径中基因的mRNA表达的代偿性增加，与野生型小鼠相比，10-12周龄的CA-AMPK-α 1转基因小鼠表现出正常的肝脏甘油三酯含量。但尚不清楚白色脂肪组织中的脂肪生成基因表达是否也发生了变化。在这里，我们的特点是在白色脂肪组织中的胆固醇和脂肪酸生物合成途径的主要脂肪生成基因的mRNA表达谱。数据显示，肝脏中AMPK的短期慢性活化引起肝脏中由于Srebp-2的诱导而引起的脂肪生成基因表达的显著补偿性增加和白色脂肪组织中由于Srebp-1c的上调而引起的脂肪生成基因表达的显著补偿性增加。这些结果支持的概念，除了其公认的脂肪储存的功能，脂肪组织可以在脂肪酸合成中发挥适应性作用时，脂肪酸合成严重减少肝脏，在哺乳动物中的主要脂肪生成器官。(C)2011 Elsevier Inc. All rights reserved.
We previously described a line of transgenic mice selectively expressing constitutively active AMPK-alpha 1 under the control of liver-specific human apoE promoter with the hepatic control region sequence. In the short-term activation, the CA-AMPK-alpha 1 transgenic mice at age 10-12 weeks exhibited normal hepatic triglyceride content as compared to wild-type mice due to compensatory increase in mRNA expression of genes in the cholesterol and fatty acid synthesis pathways. But it was not known whether the lipogenic gene expression in white adipose tissue also changed. Here we characterized mRNA expression profile of main lipogenic genes in the cholesterol and fatty acid biosynthesis pathway in white adipose tissue. The data show that short-term chronic activation of AMPK in liver caused marked compensatory increase in lipogenic gene expression both in liver due to induction of Srebp-2 and in white adipose tissue due to upregulation of Srebp-lc. These results support the notion that in addition to its well-recognized function for fat storage adipose tissue can play an adaptive role in fatty acid synthesis when fatty acid synthesis is severely reduced in liver, the main lipogenic organ in mammals. (C) 2011 Elsevier Inc. All rights reserved.