Unilever R&D Discover, Colworth Park, Bedfordshire MK44 1LQ, United Kingdom.
Arch Physiol Biochem. 2012 Jul;118(3):112-20. doi: 10.3109/13813455.2012.654611. Epub 2012 Feb 21.
The effect of hypoxia on global gene expression in human adipocytes has been examined using DNA microarrays. Adipocytes (Zen-Bio, day 12 post-differentiation) were exposed to hypoxia (1% O(2)) or 'normoxia' (21% O(2)) for 24 h and extracted RNA probed with Agilent arrays containing 41,152 probes. A total of 1346 probes were differentially expressed (>2.0-fold change, P < 0.01) in response to hypoxia; 650 genes were up-regulated (including LEP, IL6, VEGF, ANGPTL4) and 650 down-regulated (including ADIPOQ, UCP2). Major genes not previously identified as hypoxia-sensitive in adipocytes include AQP3, FABP3, FABP5 and PPARGC1A. Ingenuity analysis indicated that several pathways and functions were modulated by hypoxia, including glucose utilization, lipid oxidation and cell death. Network analysis indicated a down-regulation of p38/MAPK and PGC-1α signalling in the adipocytes. It is concluded that hypoxia has extensive effects on human adipocyte gene expression, consistent with low O(2) tension underlying adipose tissue dysfunction in obesity.
采用 DNA 微阵列研究了缺氧对人脂肪细胞中整体基因表达的影响。将脂肪细胞（Zen-Bio，分化后第 12 天）暴露于缺氧（1% O2）或“常氧”（21% O2）中 24 小时，并使用 Agilent 微阵列提取 RNA 进行探测，该微阵列包含 41,152 个探针。共有 1346 个探针对缺氧表现出差异表达（>2.0 倍变化，P < 0.01）；650 个基因上调（包括 LEP、IL6、VEGF、ANGPTL4），650 个基因下调（包括 ADIPOQ、UCP2）。以前在脂肪细胞中未被确定为缺氧敏感的主要基因包括 AQP3、FABP3、FABP5 和 PPARGC1A。Ingenuity 分析表明，几种途径和功能受到缺氧的调节，包括葡萄糖利用、脂质氧化和细胞死亡。网络分析表明，脂肪细胞中 p38/MAPK 和 PGC-1α 信号通路受到下调。结论是，缺氧对人脂肪细胞基因表达有广泛的影响，这与肥胖症中脂肪组织功能障碍的低氧张力相一致。
