Reduced IRS-2 and GLUT4 expression in PPARγ2-induced adipocytes derived from C/EBPβ and C/EBPδ-deficient mouse embryonic fibroblasts
Reduced IRS-2 and GLUT4 expression in PPARγ2-induced adipocytes derived from C/EBPβ and C/EBPδ-deficient mouse embryonic fibroblasts
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C/EBPβ 和 C/EBPδ 缺陷的小鼠胚胎成纤维细胞来源的 PPARγ2 诱导的脂肪细胞中 IRS-2 和 GLUT4 表达减少
作者：
Hiroyasu Yamamoto;S. Kurebayashi;T. Hirose;H. Kouhara;S. Kasayama
在脂肪组织中，细胞在向成熟脂肪细胞分化的过程中获得了对胰岛素作出反应和表达编码脂肪酸结合蛋白（422/aP2）、脂蛋白脂肪酶（LPL）、脂素和葡萄糖转运蛋白4 （GLUT4）等基因的能力。人们已经认识到过氧化物酶体增殖激活受体γ (PPARγ)和CCAAT/增强子结合蛋白（C/ ebp）在脂肪细胞分化中起关键作用。然而，尚不确定PPARγ或哪种C/EBP参与了这些特征的获得。我们将PPARγ2引入到C/EBPβ/δ-双缺陷小鼠胚胎成纤维细胞（MEFs）中，然后用其配体刺激，以确定C/EBPβ和C/EBPδ在脂肪细胞分化过程中表型获取中的作用。这一过程导致这些mef分化为成熟的脂肪细胞，在形态上与野生型mef相似。然而，C/EBPβ/δ-缺陷MEFs衍生的脂肪细胞GLUT4和adipsin mRNA的表达低于野生型MEFs，尽管aP2和LPL mRNA水平在两种类型中相似。C/EBPβ/δ-缺陷脂肪细胞的胰岛素受体底物2 （IRS-2）表达量也低于野生型mef脂肪细胞，而胰岛素受体和IRS-1的表达量相似。最后，在C/EBPβ/δ-缺陷细胞中，胰岛素反应性2-脱氧葡萄糖摄取较低。因此，可以证明C/EBPβ和C/EBPδ参与了IRS-2和GLUT4表达的获得以及脂肪细胞分化过程中胰岛素敏感的葡萄糖摄取。
In adipose tissue, the ability of cells to respond to insulin and to express genes such as those encoding fatty-acid-binding protein (422/aP2), lipoprotein lipase (LPL), adipsin and glucose transporter 4 (GLUT4) is acquired during their differentiation into mature adipocytes. It has been recognized that peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs) play critical roles in adipocyte differentiation. However, it remained uncertain whether PPARγ or which C/EBP is involved in the acquisition of these characteristics. We introduced PPARγ2 into C/EBPβ/δ-double deficient mouse embryonic fibroblasts (MEFs), followed by stimulation with its ligands, in order to define the roles of C/EBPβ and C/EBPδ in phenotypic acquisition during adipocyte differentiation. This procedure resulted in differentiation of these MEFs into mature adipocytes morphologically similar to wild-type MEFs. However, the adipocytes derived from the C/EBPβ/δ-deficient MEFs showed lower expression of GLUT4 and adipsin mRNA than those derived from wild-type MEFs, although aP2 and LPL mRNA levels were similar in both types. The C/EBPβ/δ-deficient adipocytes also expressed lower amounts of insulin receptor substrate 2 (IRS-2) than the adipocytes derived from wild-type MEFs, whereas the amounts of insulin receptor and IRS-1 were similar. Finally, insulin-responsive 2-deoxyglucose uptake was lower in the C/EBPβ/δ-deficient cells. It could thus be demonstrated that C/EBPβ and C/EBPδ are involved in the acquisition of IRS-2 and GLUT4 expression as well as in insulin-sensitive glucose uptake during adipocyte differentiation.
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DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Toscani,A;Soprano,DR;Soprano,KJ
通讯作者：
Soprano,KJ
DOI：
10.1073/pnas.88.19.8465
发表时间：
1991-10-01
影响因子：
11.1
作者：
CHENEVAL, D;CHRISTY, RJ;LANE, MD
通讯作者：
LANE, MD
影响因子：
10.5
作者：
E. Rosen;C. Walkey;P. Puigserver;B. Spiegelman
通讯作者：
E. Rosen;C. Walkey;P. Puigserver;B. Spiegelman
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DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sadowski,HB;Wheeler,TT;Young,DA
通讯作者：
Young,DA
DOI：
10.1172/jci1244
发表时间：
1998
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Zhidan Wu;Yuhong Xie;R. Morrison;N. Bucher;S. Farmer
通讯作者：
Zhidan Wu;Yuhong Xie;R. Morrison;N. Bucher;S. Farmer