Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes

被引:303
|
作者
Wang, Bohan [1 ]
Wood, I. Stuart [1 ]
Trayhurn, Paul [1 ]
机构
[1] Univ Liverpool, Sch Clin Sci, Liverpool Ctr Nutrit Genom & Liverpool Obes Res N, Clin Dept,Obes Biol Unit, Liverpool L69 3GA, Merseyside, England
来源
基金
英国生物技术与生命科学研究理事会;
关键词
adipokines; adipose tissue; hypoxia; inflammation; obesity; metabolic syndrome;
D O I
10.1007/s00424-007-0301-8
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The effect of hypoxia, induced by incubation under low (1%) oxygen tension or by exposure to CoCl2, on the expression and secretion of inflammation-related adipokines was examined in human adipocytes. Hypoxia led to a rapid and substantial increase (greater than sevenfold by 4 h of exposure to 1% O-2) in the hypoxia-sensitive transcription factor, HIF-1 alpha, in human adipocytes. This was accompanied by a major increase (up to 14-fold) in GLUT1 transporter mRNA level. Hypoxia (1% O-2 or CoCl2) led to a reduction (up to threefold over 24 h) in adiponectin and haptoglobin mRNA levels; adiponectin secretion also decreased. No changes were observed in TNF alpha expression. In contrast, hypoxia resulted in substantial increases in FIAF/angiopoietin-like protein 4, IL-6, leptin, MIF, PAI-1 and vascular endothelial growth factor (VEGF) mRNA levels. The largest increases were with FIAF (maximum 210-fold), leptin (maximum 29-fold) and VEGF (maximum 23-fold); these were reversed on return to normoxia. The secretion of IL-6, leptin, MIF and VEGF from the adipocytes was also stimulated by exposure to 1% O-2. These results demonstrate that hypoxia induces extensive changes in human adipocytes in the expression and release of inflammation-related adipokines. Hypoxia may underlie the development of the inflammatory response in adipocytes, leading to obesity-associated diseases.
引用
收藏
页码:479 / 492
页数:14
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