Visfatin in adipocytes is upregulated by hypoxia through HIFIα-dependent mechanism
Visfatin in adipocytes is upregulated by hypoxia through HIFIα-dependent mechanism
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DOI：
10.1016/j.bbrc.2006.07.083
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发表时间：
2006-10-27
影响因子：
3.1
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Segawa, Katsumori;Fukuhara, Atsunori;Shimomura, Iichiro
肥胖与代谢紊乱有关，如胰岛素抵抗。Visfatin是一种脂肪衍生的分泌因子，可发挥类似胰岛素的作用。肥胖患者血浆内脂素水平和脂肪组织内脂素mRNA水平均升高。然而，肥胖症患者脂肪组织中内脂素mRNA的诱导机制尚不清楚。最近的研究报道，肥胖的脂肪组织是缺氧的。在本研究中，我们研究了低氧对脂肪细胞内脂素基因表达的影响。低氧可增加visfatin基因的表达。去铁胺和氯化钴，这两种模拟低氧的化合物，也增加了visfatin的mRNA水平。低氧诱导因子1α(HIF1α)的稳定剂二甲氧烯丙基甘氨酸可模拟低氧诱导的visfatin表达上调，而HIF1的抑制剂Yc1可阻断低氧诱导的visfatin mRNA表达上调。我们在小鼠Visfatin启动子中发现了两个功能性缺氧反应元件(HRE)。低氧处理和HIF1α的过表达增加了启动子的活性，HRE突变钝化了低氧诱导的内脂素启动子的激活。我们的结果表明，肥胖脂肪组织中visfatin mRNA的表达上调是通过低氧激活HIF1α途径实现的。(C)2006 Elsevier Inc.保留所有权利。
Obesity is associated with metabolic disorders, such as insulin resistance. Visfatin is an adipose-derived secretory factor to exert insulin-mimetic effects. Plasma visfatin levels and mRNA levels of visfatin in adipose tissues are increased in obesity. However, the mechanism that mediates induction of visfatin mRNA in adipose tissue of obesity remains unknown. Recent studies have reported that fat tissue is hypoxia in obesity. In this study, we investigated the effects of hypoxia on mRNA expression of visfatin in adipocytes. Hypoxia increased visfatin mRNA expression. Desferoxamine and Cobaltous chloride, two hypoxia mimetic compounds, also increased visfatin mRNA levels. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1 alpha (HIF1 alpha), mimicked the hypoxia-mediated upregulation of visfatin, and YC1, an inhibitor of HIF1 cancelled the hypoxia-induced upregulation of visfatin mRNA. We identified two functional hypoxia responsive elements (HRE) in mouse visfatin promoter. Hypoxic treatment and overexpression of HIF1 alpha increased the promoter activity, and mutation of the HRE blunted hypoxia-induced activation of visfatin promoter. Our results suggest that visfatin mRNA expression is upregulated in the fat tissue of obesity through the activation of HIF1 alpha pathway due to hypoxia. (c) 2006 Elsevier Inc. All rights reserved.