Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice
Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice
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DOI：
10.1152/ajpendo.00435.2007
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发表时间：
2007-10-01
影响因子：
5.1
通讯作者：
He, Qing
中科院分区：
文献类型：
--
作者：
Ye, Jianping;Gao, Zhanguo;He, Qing
慢性炎症和脂联素减少在肥胖者的白色脂肪组织中广泛存在。然而，这些变化的原因仍有待确定。在这项研究中，我们提供了实验证据，表明肥胖小鼠的脂肪组织中存在缺氧情况，并且脂肪缺氧可能导致内分泌改变。通过间质氧分压（Po - 2）降低、缺氧探针信号增强以及ob/ob小鼠缺氧反应基因表达升高，证明了脂肪缺氧。通过缺氧反应基因的表达，在饮食诱导肥胖的小鼠中也证实了脂肪缺氧。在脂肪组织中，缺氧与炎症基因表达增加和脂联素表达减少有关。在饮食诱导肥胖的小鼠中，通过热量限制减轻体重与氧合改善和炎症减轻相关。在细胞培养中，瘦小鼠的原代脂肪细胞和原代巨噬细胞中，缺氧诱导了炎症细胞因子。在3T3 - L1脂肪细胞和NIH3T3成纤维细胞中，缺氧激活了转录因子NF - κB和TNF - α基因启动子。此外，缺氧降低了脂联素的表达，并且在脂肪细胞的基因启动子中也观察到了这种降低。这些数据表明，缺氧在肥胖者脂肪组织中诱导慢性炎症和抑制脂联素方面可能具有潜在作用。
Chronic inflammation and reduced adiponectin are widely observed in the white adipose tissue in obesity. However, the cause of the changes remains to be identified. In this study, we provide experimental evidence that hypoxia occurs in adipose tissue in obese mice and that adipose hypoxia may contribute to the endocrine alterations. The adipose hypoxia was demonstrated by a reduction in the interstitial partial oxygen pressure (Po-2), an increase in the hypoxia probe signal, and an elevation in expression of the hypoxia response genes in ob/ob mice. The adipose hypoxia was confirmed in dietary obese mice by expression of hypoxia response genes. In the adipose tissue, hypoxia was associated with an increased expression of inflammatory genes and decreased expression of adiponectin. In dietary obese mice, reduction in body weight by calorie restriction was associated with an improvement of oxygenation and a reduction in inflammation. In cell culture, inflammatory cytokines were induced by hypoxia in primary adipocytes and primary macrophages of lean mice. The transcription factor NF-kappa B and the TNF-alpha gene promoter were activated by hypoxia in 3T3-L1 adipocytes and NIH3T3 fibroblasts. In addition, adiponectin expression was reduced by hypoxia, and the reduction was observed in the gene promoter in adipocytes. These data suggest a potential role of hypoxia in the induction of chronic inflammation and inhibition of adiponectin in the adipose tissue in obesity.