Evidence of impaired adipogenesis in insulin resistance
Evidence of impaired adipogenesis in insulin resistance
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DOI：
10.1016/j.bbrc.2004.03.152
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发表时间：
2004-05-14
影响因子：
3.1
通讯作者：
Smith, U
中科院分区：
文献类型：
--
作者：
Yang, XL;Jansson, PA;Smith, U
为了阐明脂肪组织和骨骼肌在胰岛素抵抗早期发展中的作用，我们采用寡核苷酸微阵列技术对2型糖尿病患者非糖尿病胰岛素抵抗一级亲属的分离脂肪细胞和骨骼肌的基因表达谱进行了表征。约600个基因和表达序列标签，显示了细胞增殖的基因表达模式，在脂肪细胞中差异表达。骨骼肌中差异表达的基因主要与细胞信号转导和转录调控有关。为了验证微阵列的发现，我们研究了参与脂肪形成的基因的表达。脂肪组织中Wnt信号传导基因WNT 1、FZD 1、DVL 1、GSK 3 β、β-连环蛋白和TCF 1以及脂肪形成转录因子C/EBPalpha和β和δ、PPARgamma和SREBP-1的表达降低。与终末分化相关的脂肪特异性蛋白质（如脂联素和aP 2）的表达在脂肪组织和从部分活检分离的脂肪细胞中均降低。在胰岛素抵抗的亲属中，脂肪细胞增大，并且细胞大小与Wnt信号传导基因、脂联素和aP 2的表达呈负相关。我们的研究结果表明，胰岛素抵抗与脂肪形成受损有关。(C)2004年爱思唯尔公司All rights reserved.
To elucidate the roles of adipose tissue and skeletal muscle in the early development of insulin resistance, we characterized gene expression profiles of isolated adipose cells and skeletal muscle of non-diabetic insulin-resistant first-degree relatives of type 2 diabetic patients using oligonucleotide microarrays. About 600 genes and expressed sequence tags, which displayed a gene expression pattern of cell proliferation, were differentially expressed in the adipose cells. The differentially expressed genes in the skeletal muscle were mostly related to the cellular signal transduction and transcriptional regulation. To verify the microarray findings, we studied expression of genes participating in adipogenesis. The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3beta, beta-catenin, and TCF1, and adipogenic transcription factors, C/EBPalpha and beta and delta, PPARgamma, and SREBP-1, was reduced in the adipose tissue. The expression of adipose-specific proteins related to terminal differentiation, such as adiponectin and aP2, was reduced both in the adipose tissue and in the adipose cells isolated from portions of the biopsies. The adipose cells were enlarged in the insulin-resistant relatives and the cell size inversely correlated with the expression of the Wnt signaling genes, adiponectin, and aP2. Our findings suggest that insulin resistance is associated with an impaired adipogenesis. (C) 2004 Elsevier Inc. All rights reserved.