Thiazolidinediones downregulate stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes
Thiazolidinediones downregulate stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes
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DOI：
10.2337/diabetes.46.12.2115
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发表时间：
1997-12-01
期刊：
影响因子：
7.7
通讯作者：
Kishimoto, T
中科院分区：
文献类型：
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作者：
Kurebayashi, S;Hirose, T;Kishimoto, T
噻唑烷二酮类药物（TZDs）具有增强胰岛素敏感性的作用，因为过氧化物酶体增殖物激活受体-γ TZDs的受体PPAR-gamma主要在脂肪细胞中表达，我们尝试在小鼠3 T3-L1脂肪细胞中寻找TZD的靶基因，通过mRNA差异显示方法，得到一条被曲格列酮抑制的条带，其对应于硬脂酰辅酶A去饱和酶1（SCD 1）基因的部分序列，Troglitazone以剂量依赖性方式显著降低3 T3-L1脂肪细胞中SCD 1 mRNA水平。吡格列酮也抑制了SCD 1 mRNA的表达，而WY-14，643没有明显的作用。曲格列酮和吡格列酮均提高了肉豆蔻酸（C14：0）、棕榈酸（C16：0）和硬脂酸（C18：0）的组成（重量百分比），但降低了Delta（9）-顺式去饱和脂肪酸的组成，如肉豆蔻脑酸（C14：1，Delta（9））、棕榈油酸（C16：1 Delta（9））、油酸（C14：1，Delta（9））和亚油酸（C18：2，Delta（9），（12））。这些结果表明TZDs通过下调SCD 1酶基因表达来抑制3 T3-L1脂肪细胞中的SCD 1活性。
Thiazolidinediones (TZDs) are known to have potent increases of insulin sensitivity, Because peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a receptor for TZDs, is mainly expressed in adipocytes, we tried to search the TZD-targeted genes in mouse 3T3-L1 adipocytes, By the mRNA differential display method, one band repressed by troglitazone was obtained, which corresponded to the partial sequences of the stearoyl-CoA desaturase 1 (SCD1) gene, Troglitazone dramatically decreased SCD1 mRNA levels in 3T3-L1 adipocytes in a dose-dependent manner. Pioglitazone also repressed the SCD1 mRNA expression, whereas WY-14,643 had no apparent effect. Both troglitazone and pioglitazone raised the composition (weight percentage) of myristic acid (C14:0), palmitic acid (C16:0), and stearic acid (C18:0), but lowered the composition of the Delta(9)-cis desaturated fatty acids such as myristoleic acid (C14:1, Delta(9)), palmitoleic acid (C16:1 Delta(9)), oleic acid (C14:1, Delta(9)), and linoleic acid (C18:2, Delta(9), (12)). These results indicate that TZDs repress SCD1 activity in 3T3-L1 adipocytes via downregulating SCD1 enzyme gene expression.