Wang Bohan, Wood I Stuart, Trayhurn Paul
Obesity Biology Unit (Liverpool Centre for Nutritional Genomics and Liverpool Obesity Research Network), School of Clinical Sciences, University Clinical Departments, University of Liverpool, Liverpool, UK.
Pflugers Arch. 2007 Dec;455(3):479-92. doi: 10.1007/s00424-007-0301-8. Epub 2007 Jul 3.
The effect of hypoxia, induced by incubation under low (1%) oxygen tension or by exposure to CoCl(2), 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-1alpha, in human adipocytes. This was accompanied by a major increase (up to 14-fold) in GLUT1 transporter mRNA level. Hypoxia (1% O(2) or CoCl(2)) 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 TNFalpha 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.
在人脂肪细胞中，研究了低氧（1%氧张力孵育）或暴露于氯化钴诱导的缺氧对炎症相关脂肪因子表达和分泌的影响。缺氧导致人脂肪细胞中缺氧敏感转录因子HIF-1α迅速大幅增加（暴露于1% O₂ 4小时后增加超过7倍）。这伴随着GLUT1转运蛋白mRNA水平的大幅增加（高达14倍）。缺氧（1% O₂ 或氯化钴）导致脂联素和触珠蛋白mRNA水平降低（24小时内高达3倍）；脂联素分泌也减少。未观察到TNFα表达的变化。相反，缺氧导致FIAF/血管生成素样蛋白4、IL-6、瘦素、MIF、PAI-1和血管内皮生长因子（VEGF）mRNA水平大幅增加。增加幅度最大的是FIAF（最大210倍）、瘦素（最大29倍）和VEGF（最大23倍）；恢复到常氧后这些增加被逆转。暴露于1% O₂ 也刺激了脂肪细胞中IL-6、瘦素、MIF和VEGF的分泌。这些结果表明，缺氧在人脂肪细胞中诱导炎症相关脂肪因子的表达和释放发生广泛变化。缺氧可能是脂肪细胞炎症反应发展的基础，导致肥胖相关疾病。
