Identification of hypoxia-induced genes in human SGBS adipocytes by microarray analysis.
Identification of hypoxia-induced genes in human SGBS adipocytes by microarray analysis.
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DOI：
10.1371/journal.pone.0026465
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Drexel H
中科院分区：
文献类型：
--
作者：
Geiger K;Leiherer A;Muendlein A;Stark N;Geller-Rhomberg S;Saely CH;Wabitsch M;Fraunberger P;Drexel H
脂肪组织中的缺氧被认为参与慢性轻度炎症的发展，其在肥胖症中可进一步导致胰岛素抵抗。缺氧对脂肪细胞基因表达的影响似乎在肥胖症中观察到的这种炎症反应中起着核心作用。然而，缺氧对人类脂肪细胞转录变化的整体影响尚不清楚。因此，我们比较了人GBS脂肪细胞在常氧和低氧条件下的基因表达谱，以检测脂肪细胞中的低氧反应基因，通过使用全人类基因组芯片。微阵列分析显示，在低氧水平下孵育细胞后，有超过500种显著差异调节的mRNA。为了进一步了解生物学过程，根据功能对缺氧16小时后的缺氧调节基因进行了分类。我们确定了一个丰富的基因参与重要的生物过程，如糖酵解，缺氧反应，调节细胞成分的运动，营养水平的反应，调节细胞迁移，转录调节因子的活性。实时PCR证实了8个基因在缺氧3、6和16小时后持续上调。对于脂肪细胞，缺氧诱导的这些基因的调节在这里首次显示。此外，在这八个基因中的六个中，我们在近端启动子中鉴定了HIF应答元件，其特异于HIF转录因子家族成员HIF 1A和HIF 2A。在本研究中，我们证明了缺氧对SGBS脂肪细胞的基因表达有广泛的影响。此外，已鉴定的低氧调节基因可能参与肥胖、2型糖尿病发病率和代谢综合征的调节。
Hypoxia in adipose tissue is suggested to be involved in the development of a chronic mild inflammation, which in obesity can further lead to insulin resistance. The effect of hypoxia on gene expression in adipocytes appears to play a central role in this inflammatory response observed in obesity. However, the global impact of hypoxia on transcriptional changes in human adipocytes is unclear. Therefore, we compared gene expression profiles of human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes under normoxic or hypoxic conditions to detect hypoxia-responsive genes in adipocytes by using whole human genome microarrays. Microarray analysis showed more than 500 significantly differentially regulated mRNAs after incubation of the cells under low oxygen levels. To gain further insight into the biological processes, hypoxia-regulated genes after 16 hours of hypoxia were classified according to their function. We identified an enrichment of genes involved in important biological processes such as glycolysis, response to hypoxia, regulation of cellular component movement, response to nutrient levels, regulation of cell migration, and transcription regulator activity. Real-time PCR confirmed eight genes to be consistently upregulated in response to 3, 6 and 16 hours of hypoxia. For adipocytes the hypoxia-induced regulation of these genes is shown here for the first time. Moreover in six of these eight genes we identified HIF response elements in the proximal promoters, specific for the HIF transcription factor family members HIF1A and HIF2A. In the present study, we demonstrated that hypoxia has an extensive effect on gene expression of SGBS adipocytes. In addition, the identified hypoxia-regulated genes are likely involved in the regulation of obesity, the incidence of type 2 diabetes, and the metabolic syndrome.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
14.9
作者：
Benita Y;Kikuchi H;Smith AD;Zhang MQ;Chung DC;Xavier RJ
通讯作者：
Xavier RJ
影响因子：
20.1
作者：
Bouloumié, A;Drexler, HCA;Busse, R
通讯作者：
Busse, R
影响因子：
4.8
作者：
Fain, JN;Madan, AK;Bahouth, SW
通讯作者：
Bahouth, SW
DOI：
10.1016/j.ecl.2008.07.002
发表时间：
2008-09
影响因子：
4.5
作者：
Halberg, Nils;Wernstedt-Asterholm, Ingrid;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.