NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression.
NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression.
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NR4A1 通过增强 GATA2 和 p53 表达来延迟脂肪细胞分化或成熟
DOI：
10.1111/jcmm.13715
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发表时间：
2018-10
影响因子：
5.3
通讯作者：
Liu YT
中科院分区：
文献类型：
--
作者：
Qin DD;Yang YF;Pu ZQ;Liu D;Yu C;Gao P;Chen JC;Zong C;Zhang YC;Li X;Wang XD;Liu YT
核受体亚家族4 A组成员1(NR4A1)是一种具有多种功能的孤儿核受体。有报道称，NR4A1作为一种转录激活因子，与糖脂代谢密切相关。本研究的目的是研究NR4A1在脂肪形成中的调节作用，并探讨其潜在的机制。用实时定量聚合酶链式反应和Western blotting分析脂肪合成和动员相关基因在体内和体外的表达。采用双荧光素酶报告实验研究NR4A1的调控机制。我们的体内研究数据证实，高脂饮食喂养的NR4A1基因敲除(KO)小鼠更容易肥胖，并且KO小鼠PPARγ和Fas的基因表达水平高于对照组；我们的体外研究数据表明，NR4A1在3T3-L1前脂肪细胞中过表达抑制脂肪形成。此外，NR4A1促进GATA结合蛋白2(GATA2)的表达，进而抑制过氧化物酶体增殖物激活受体γ(PPARγ)；NR4A1通过上调P53来抑制固醇调节元件结合转录因子1(SREBP1)及其下游基因脂肪酸合成酶(Fas)。NR4A1通过增强GATA2和P53的表达来抑制脂肪细胞的分化和脂质堆积。
Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR4A1 in adipogenesis and explore the underlying mechanisms. Quantitative real‐time PCR and Western blotting were used to analyse the expression of genes involved in synthesis and mobilization of fats in vivo and in vitro. Dual‐luciferase reporter assay was conducted to study the regulatory mechanisms of NR4A1. Our data from in vivo study confirmed that NR4A1 knockout (KO) mice fed with high‐fat diet were more prone to obesity, and gene expression levels of PPARγ and FAS were increased in KO mice compared to controls; our data from in vitro study showed that NR4A1 overexpression in 3T3‐L1 pre‐adipocytes inhibited adipogenesis. Moreover, NR4A1 enhanced GATA binding protein 2 (GATA2) expression, which in turn inhibited peroxisome proliferator‐activated receptor γ (PPARγ); NR4A1 inhibited sterol regulatory element binding transcription factor 1 (SREBP1) and its downstream gene fatty acid synthase (FAS) by up‐regulating p53. NR4A1 inhibits the differentiation and lipid accumulation of adipocytes by enhancing the expression of GATA2 and p53.
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DOI：
10.1016/j.jsbmb.2015.04.016
发表时间：
2016-03
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Safe S;Jin UH;Morpurgo B;Abudayyeh A;Singh M;Tjalkens RB
通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/j.bbalip.2011.09.017
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2012-05
期刊：
Biochimica et biophysica acta
影响因子：
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通讯作者：
Semenkovich CF
DOI：
10.1007/978-1-4939-2929-0_17
发表时间：
2015-01-01
期刊：
METHODS IN MOUSE ATHEROSCLEROSIS
影响因子：
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作者：
Vinue, Angela;Gonzalez-Navarro, Herminia
通讯作者：
Gonzalez-Navarro, Herminia
DOI：
10.1210/me.2008-0161
发表时间：
2008-12
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
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作者：
Chao LC;Bensinger SJ;Villanueva CJ;Wroblewski K;Tontonoz P
通讯作者：
Tontonoz P