Hypoxia potentiates tumor necrosis factor-α induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes
Hypoxia potentiates tumor necrosis factor-α induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes
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DOI：
10.1016/j.bbrc.2015.04.020
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发表时间：
2015-05-29
影响因子：
3.1
通讯作者：
Battegay, Edouard J.
中科院分区：
文献类型：
--
作者：
Bhattacharya, Indranil;Dominguez, Ana Perez;Battegay, Edouard J.
肥胖症涉及脂肪组织缺氧和低度慢性炎症。我们研究了缺氧对白色和棕色脂肪细胞对TNF-α的炎症反应的影响。在对TNF-α的反应中，诱导酶iNOS和考克斯-2的表达在缺氧期间显著且选择性增强，而在常氧下仅中度增强。其产物亚硝酸盐和野牡丹碱E（2）的水平相应升高。选择性考克斯-2抑制剂NS 398可降低亚硝酸盐水平。PGC-1 α（一种参与线粒体生物合成的转录辅激活因子）和PPAR-gamma（一种参与脂肪细胞稳态的转录因子）的表达在缺氧期间被TNF-α降低。这些结果表明，缺氧增强了白色和棕色脂肪细胞中TNF-α的炎症反应，并下调了参与脂肪细胞功能的转录因子。(C)2015 Elsevier Inc. All rights reserved.
Obesity involves hypoxic adipose tissue and low-grade chronic inflammation. We investigated the impact of hypoxia on inflammatory response to TNF-alpha in white and brown adipocytes. In response to TNF-alpha, the expression of the inducible enzymes iNOS and COX-2 was prominently and selectively potentiated during hypoxia while only moderately under normoxia. Levels of their products, nitrite and prostaglandinE(2) were elevated accordingly. NS398, a selective COX-2 inhibitor, reduced nitrite levels. The expression of PGC-1 alpha, a transcriptional co-activator involved in mitochondrial biogenesis, and PPAR-gamma, a transcription factor involved in adipocyte homeostasis, was reduced by TNF-alpha during hypoxia. These results suggest that hypoxia potentiates the inflammatory response by TNF-alpha in both white and brown adipocytes and downregulates the transcription factors involved in adipocyte function. (C) 2015 Elsevier Inc. All rights reserved.