A translation repressor, 4E-BP1, regulates the triglyceride level in rat liver during protein deprivation
A translation repressor, 4E-BP1, regulates the triglyceride level in rat liver during protein deprivation
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翻译抑制因子 4E-BP1 在蛋白质剥夺期间调节大鼠肝脏中的甘油三酯水平
DOI：
10.1152/ajpendo.00464.2019
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发表时间：
2020
影响因子：
5.1
通讯作者：
Minami Shiro
中科院分区：
文献类型：
--
作者：
Toyoshima Yuka;Yoshizawa Fumiaki;Tokita Reiko;Taguchi Yusuke;Takahashi Shin-Ichiro;Kato Hisanori;Minami Shiro
蛋白质剥夺已被证明会在人类和动物中诱发脂肪肝，但这种诱导的分子机制在很大程度上还不清楚。我们以前的研究表明，低蛋白饮食会增加大鼠肝脏中真核翻译起始因子4E结合蛋白1(4E-BP1)蛋白和甘油三酯(TG)的水平。已知4E-BP1通过与eIF4E结合来抑制翻译。也有证据表明，4E-BP1调节脂质代谢。在这里，我们研究了4E-BP1在蛋白质剥夺大鼠肝脏中甘油三酯积累的作用。低蛋白饲料在1d内迅速增加肝脏4E-BP1mRNA水平，随后诱导肝脏TG蓄积。肝脏4E-BP1基因敲除可减轻低蛋白饮食诱导的大鼠肝脏甘油三酯蓄积。4E-BP1基因敲除还增加了低蛋白饮食大鼠肝脏中脂肪酸氧化调节因子肉碱棕榈酰基转移酶1A(CPT1A)的蛋白水平。这些结果表明，低蛋白饮食增加了4E-BP1的数量，导致TG在大鼠肝脏中积累。因此，我们认为4E-BP1在蛋白剥夺诱导肝脏脂肪变性中起重要作用。
Protein deprivation has been shown to induce fatty liver in humans and animals, but the molecular mechanisms underlying such induction are largely unknown. Our previous studies have shown that a low-protein diet increases eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) protein and triglyceride (TG) levels in rat liver. 4E-BP1 is known to repress translation by binding to eIF4E. There is also evidence indicating that 4E-BP1 regulates lipid metabolism. Here, we examined the role of 4E-BP1 on TG accumulation in the livers of rats under protein deprivation. The low-protein diet rapidly increased the hepatic 4E-BP1 mRNA level within 1 day, followed by the induction of hepatic TG accumulation. The knockdown of hepatic 4E-BP1 attenuated the TG accumulation in rat liver induced by the low-protein diet. 4E-BP1 knockdown also increased the protein level of carnitine palmitoyltransferase 1A (CPT1A), a regulator of fatty acid oxidation, in the liver of rats fed a low-protein diet. These results indicate that a low-protein diet increases the amount of 4E-BP1, leading to TG accumulation in rat liver. We thus conclude that 4E-BP1 plays an important role in inducing hepatic steatosis under protein deprivation.