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噻唑烷二酮类药物对3T3-L1脂肪细胞中硬脂酰辅酶A去饱和酶基因的差异调节

Differential regulation of the stearoyl-CoA desaturase genes by thiazolidinediones in 3T3-L1 adipocytes.

作者信息

Kim Y C, Gomez F E, Fox B G, Ntambi J M

机构信息

Departments of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI 53706, USA.

出版信息

J Lipid Res. 2000 Aug;41(8):1310-6.

PMID:10946019
Abstract

Two stearoyl-CoA desaturase (SCD) isoforms can be expressed during the differentiation of 3T3-L1 preadipocytes into adipocytes. Here we report on the effects of the peroxisome proliferator-activated receptor gamma ligand troglitazone (TRO) on scd1 and scd2 mRNA levels as determined by Northern blotting, on SCD protein expression as determined by Western blotting, and on total lipid composition as determined by GC during differentiation. In preadipocytes, scd1 mRNA and SCD protein were not detected, whereas scd2 mRNA was detected. These cells have high levels of palmitate (16:0), stearate (18:0), and monounsaturated oleate (Delta(9)-18:1) and low levels of monounsaturated palmitoleate (Delta(9)-16:1). In MDI (methylisobutylxanthine, dexamethasone, and insulin)-treated cells, scd1 mRNA and SCD protein were increased approximately 100-fold relative to preadipocyte levels, the scd2 mRNA level was increased 2-fold, Delta(9)-16:1 was increased approximately 20-fold, and 18:0 was decreased approximately 3-fold. In TRO-treated cells, the scd1 mRNA level was lower than that observed in preadipocytes, while the scd2 mRNA level was similar. TRO also decreased scd1 mRNA in primary adipocytes. The TRO-treated cells contained a Delta(9)-18:1 level typical of MDI-treated cells whereas, conversely, these cells also contained a low Delta(9)-16:1 level typical of preadipocytes. The implications of these correlations for the regulatory and enzymatic mechanism(s) used to establish and maintain lipid composition are discussed.

摘要

在3T3-L1前脂肪细胞分化为脂肪细胞的过程中,可表达两种硬脂酰辅酶A去饱和酶(SCD)亚型。在此,我们报告了过氧化物酶体增殖物激活受体γ配体曲格列酮(TRO)对scd1和scd2 mRNA水平(通过Northern印迹法测定)、SCD蛋白表达(通过Western印迹法测定)以及分化过程中总脂质组成(通过气相色谱法测定)的影响。在前脂肪细胞中,未检测到scd1 mRNA和SCD蛋白,而检测到了scd2 mRNA。这些细胞中棕榈酸(16:0)、硬脂酸(18:0)和单不饱和油酸(Δ9-18:1)水平较高,而单不饱和棕榈油酸(Δ9-16:1)水平较低。在经MDI(甲基异丁基黄嘌呤、地塞米松和胰岛素)处理的细胞中,scd1 mRNA和SCD蛋白相对于前脂肪细胞水平增加了约100倍,scd2 mRNA水平增加了2倍,Δ9-16:1增加了约20倍,18:0减少了约3倍。在经TRO处理的细胞中,scd1 mRNA水平低于在前脂肪细胞中观察到的水平,而scd2 mRNA水平相似。TRO还降低了原代脂肪细胞中的scd1 mRNA。经TRO处理的细胞含有MDI处理细胞典型的Δ9-18:1水平,而相反,这些细胞也含有前脂肪细胞典型的低Δ9-16:1水平。讨论了这些相关性对于用于建立和维持脂质组成的调节和酶促机制的意义。

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