Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid
Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid
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DOI：
10.1194/jlr.m400348-jlr200
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发表时间：
2005-01-01
影响因子：
6.5
通讯作者：
Drevon, CA
中科院分区：
文献类型：
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作者：
Haugen, F;Zahid, N;Drevon, CA
抵抗素基因在脂肪细胞中表达，并编码一种被认为与肥胖和 2 型糖尿病有关的蛋白质。血浆 FFA 增加与胰岛素抵抗相关。我们检查了单独的 FFA 对培养的鼠 3T3-L1 脂肪细胞中抵抗素 mRNA 表达的影响。测试的 FFA 不会增加抵抗素表达，而花生四烯酸 (AA) 和二十碳五烯酸 (EPA) 都会降低抵抗素 mRNA 水平。 AA 是迄今为止最有效的 FEN，在 60-250 muM 浓度下，可将抵抗素 mRNA 水平降低至对照的 20%。环氧合酶-1 和丝裂原激活蛋白激酶激酶的选择性抑制剂可以抵消 AA 诱导的抵抗素 mRNA 水平的降低。甾醇调节元件结合蛋白-1a (SREBP-1a) 的瞬时过表达激活了抵抗素启动子，但在 AA 暴露后，与 65 kDa 成熟的 SREBP-1 相似的丰度没有减少。 Actinomycin D 以及放线菌酮消除了 AA 诱导的抵抗素 mRNA 水平的降低，表明对从头转录和翻译的依赖性。我们的数据表明抵抗素 mRNA 水平的降低涉及抵抗素 mRNA 分子的不稳定。 AA 和 EPA 对抵抗素表达的抑制作用可以解释摄入 PUFA 对胰岛素敏感性的有益作用。
The resistin gene is expressed in adipocytes and encodes a protein proposed to link obesity and type 2 diabetes. Increased plasma FFA is associated with insulin resistance. We examined the effect of separate FFAs on the expression of resistin mRNA in cultured murine 3T3-L1 adipocytes. The FFAs tested did not increase resistin expression, whereas both arachidonic acid (AA) and eicosapentaenoic acid (EPA) reduced resistin mRNA levels. AA was by far the most potent FEN, reducing resistin mRNA levels to similar to20% of control at 60-250 muM concentration. Selective inhibitors of cyclooxygenase-1 and of mitogen-activated protein kinase kinase counteracted AA-induced reduction in resistin mRNA levels. Transient overexpression of sterol-regulatory element binding protein-1a (SREBP-1a) activated the resistin promoter, but there was no reduction in the abundance of similar to65 kDa mature SREBP-1 after AA exposure. Actinomycin D as well as cycloheximide abolished the AA-induced reduction of resistin mRNA levels, indicating dependence on de novo transcription and translation. Our data suggest that reductions in resistin mRNA levels involve a destabilization of the resistin mRNA molecule. An inhibitory effect of AA and EPA on resistin expression may explain the beneficial effect of ingesting PUFAs on insulin sensitivity.