The mammalian target of rapamycin complex 1 regulates leptin biosynthesis in adipocytes at the level of translation:: The role of the 5′-untranslated region in the expression of leptin messenger ribonucleic acid
The mammalian target of rapamycin complex 1 regulates leptin biosynthesis in adipocytes at the level of translation:: The role of the 5′-untranslated region in the expression of leptin messenger ribonucleic acid
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DOI：
10.1210/me.2008-0148
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发表时间：
2008-10-01
影响因子：
--
通讯作者：
Kandror, Konstantin V.
中科院分区：
文献类型：
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作者：
Chakrabarti, Partha;Anno, Takatoshi;Kandror, Konstantin V.
体内脂肪细胞产生的瘦素在进食后增加，而在食物剥夺后减少。然而，控制瘦素表达的分子机制对食物摄入的反应仍然未知。在这里，我们测试的假设，瘦素在脂肪细胞中的表达调节的营养和胰岛素敏感的哺乳动物靶雷帕霉素复合物1（mTORC 1）介导的途径。mTORC 1在3 T3-L1脂肪细胞中的活性通过稳定表达组成型活性Rheb或显性负性AMP活化蛋白激酶而上调。在这两种情况下，内源性瘦素的表达显着升高的翻译水平。为了研究瘦素5 '-非翻译区（UTR）在蛋白质表达调控中的作用，我们构建了具有和不具有5'-UTR的双顺反子报告基因构建体。我们发现瘦素5 '-UTR的存在使得mRNA抵抗mTORC 1的调节。因此，似乎mTORC 1通过一种新的机制控制瘦素mRNA的翻译，该机制不需要5 '末端寡嘧啶段或5'-UTR的存在。
Leptin production by adipose cells in vivo is increased after feeding and decreased by food deprivation. However, molecular mechanisms that control leptin expression in response to food intake remain unknown. Here, we test the hypothesis that leptin expression in adipose cells is regulated by nutrient-and insulin-sensitive mammalian target of rapamycin complex 1 (mTORC1)-mediated pathway. The activity of mTORC1 in 3T3-L1 adipocytes was up-regulated by stable expression of either constitutively active Rheb or dominant-negative AMP-activated protein kinase. In both cases, expression of endogenous leptin was significantly elevated at the level of translation. To investigate the role of leptin 5'-untranslated region (UTR) in the regulation of protein expression, we created bicistronic reporter constructs with and without the 5'-UTR. We found that the presence of leptin 5'-UTR renders mRNA resistant to regulation by mTORC1. It appears, therefore, that mTORC1 controls translation of leptin mRNA via a novel mechanism that does not require the presence of either the 5'-terminal oligopyrimidine tract or the 5'-UTR.