Nitric oxide dysregulates adipocytokine expression in 3T3-L1 adipocytes
Nitric oxide dysregulates adipocytokine expression in 3T3-L1 adipocytes
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DOI：
10.1016/j.bbrc.2007.09.084
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发表时间：
2007-12-07
影响因子：
3.1
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
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作者：
Nozaki, Maiko;Fukuhara, Atsunori;Shimomura, Iichiro
肥胖与巨噬细胞浸润脂肪组织有关，而巨噬细胞是一氧化氮（NO）的重要来源。脂肪源性分泌因子脂肪细胞因子的产生失调会导致与肥胖相关的代谢紊乱。然而，尚未完全确定NO是否可能对脂肪细胞因子表达有直接影响。在这里，我们发现 NO 供体治疗下调了脂联素的基因表达和分泌，并上调了 PAI-1 和 IL-6 的 mRNA 水平。 NO 供体通过 PPAR γ 反应元件降低脂联素启动子活性。此外，NO 供体激活 JNK 和 NF-kappa B 通路，这些通路的抑制剂可以挽救 NO 介导的 PAI-1 和 IL-6 上调。对高脂喂养的肥胖小鼠脂肪组织的分析显示，PAI-1 和 IL-6 表达上调，NO 合成增加，脂联素下调。我们的结果表明，NO 合成增加可能是脂肪组织中脂肪细胞因子失调的部分原因。 (C) 2007 Elsevier Inc. 保留所有权利。
Obesity is associated with infiltration of macrophages into adipose tissue, and macrophages are an important source of nitric oxide (NO). Dysregulated production of fat-derived secretory factor, adipocytokine, leads to obesity-linked metabolic disorders. However, it has not been fully determined whether NO might have direct effects on adipocytokine expressions. Here, we show that NO donor treatment downregulated gene expression and secretion of adiponectin, and upregulated mRNA levels of PAI-1 and IL-6. NO donor reduced promoter activity of adiponectin through PPAR gamma responsive element. Moreover, NO donor activated JNK and NF-kappa B pathways, and inhibitors of these pathways rescued NO-mediated upregulation of PAI-1 and IL-6. Analysis of adipose tissue of high-fat-fed obese mice showed upregulation of PAI-1 and IL-6 expression, increased synthesis of NO, and downregulation of adiponectin. Our results suggest that increased NO synthesis might be partly responsible for dysregulation of adipocytokines in adipose tissue. (C) 2007 Elsevier Inc. All rights reserved.