EID1 suppresses lipid accumulation by inhibiting the expression of GPDH in 3T3‐L1 preadipocytes

EID1 suppresses lipid accumulation by inhibiting the expression of GPDH in 3T3‐L1 preadipocytes
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EID1通过抑制3T3-L1前脂肪细胞中GPDH的表达来抑制脂质积累

DOI:
10.1002/jcp.29567
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发表时间:
2020
影响因子:
5.6
通讯作者:
Shimokawa Noriaki
Shimokawa Noriaki
中科院分区:
生物学2区
文献类型:
--
作者:
Sato Tomohiko;Vargas Diana;Miyazaki Kakushin;Uchida Kaoru;Ariyani Winda;Miyazaki Mitsue;Okada Junichi;Lizcano Fernando;Koibuchi Noriyuki;Shimokawa Noriaki

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食物摄入和能量消耗之间的不平衡导致脂肪细胞中甘油三酯的高积累。肥胖与白色脂肪组织中脂质积累增加有关,这是发生代谢紊乱如2型糖尿病和心血管疾病的主要危险因素。这项研究强调了E1 A样分化抑制剂1(EID 1)通过下调甘油-3-磷酸脱氢酶(GPDH)在调节脂肪形成中的作用,GPDH是甘油三酯合成的关键酶,被认为是脂肪形成的标志物。通过分析DNA微阵列数据,我们发现,当EID 1在脂肪细胞分化过程中的前脂肪细胞(3 T3-L1细胞)中过表达时,EID 1通过下调GPDH抑制脂质积累。相反,EID 1不参与通过葡萄糖转运蛋白的易位调节细胞内葡萄糖。共聚焦图像分析表明,EID 1以斑点的形式定位于前脂肪细胞的细胞核中,其可能作为转录过程的调节剂而参与。我们进一步证实了EID 1能够与细胞核中的GPDH启动子序列结合。这些发现为EID 1对脂肪细胞中脂质积累的抑制作用提供了分子解释。
The imbalance between food intake and energy expenditure causes high accumulation of triglycerides in adipocytes. Obesity is related with the increased lipid accumulation in white adipose tissue, which is a major risk factor for the development of metabolic disorders, such as type 2 diabetes and cardiovascular disease. This study highlights the role of E1A‐like inhibitor of differentiation 1 (EID1) in the modulation of adipogenesis through the downregulation of glycerol‐3‐phosphate dehydrogenase (GPDH), which is a key enzyme in the synthesis of triglycerides and is considered to be a marker of adipogenesis. By analyzing DNA microarray data, we found that when EID1 is overexpressed in preadipocytes (3T3‐L1 cells) during adipocyte differentiation, EID1 inhibits lipid accumulation through the downregulation of GPDH. In contrast, EID1 is not involved in the regulation of intracellular glucose via the translocation of glucose transporter. A confocal image analysis showed that EID1 is located in the nucleus of preadipocytes in the form of speckles, which could be involved as a regulator of the transcriptional process. We further confirmed that EID1 is able to bind to the promoter sequence of GPDH in the nucleus. These findings provide a molecular explanation for the inhibitory effect of EID1 on lipid accumulation in adipocytes.
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