Stearoyl-CoA desaturase 2 is required for peroxisome proliferator-activated receptor γ expression and adipogenesis in cultured 3T3-L1 cells
Stearoyl-CoA desaturase 2 is required for peroxisome proliferator-activated receptor γ expression and adipogenesis in cultured 3T3-L1 cells
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DOI：
10.1074/jbc.m705656200
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发表时间：
2008-02-01
影响因子：
4.8
通讯作者：
Czech, Michael P.
中科院分区：
文献类型：
--
作者：
Christianson, Jennifer L.;Nicoloro, Sarah;Czech, Michael P.
基于最近的证据表明，脂肪酸合成酶和内源性产生的脂肪酸衍生物需要在3 T3-L1脂肪细胞的脂肪形成，我们进行了一个小的干扰RNA为基础的屏幕，以确定其他脂肪酸代谢酶，可能介导这种效果。在筛选的24种酶中，发现硬脂酰辅酶A去饱和酶2（SCD 2）是脂肪形成唯一且绝对必需的。值得注意的是，SCD 2还控制完全分化的3 T3-L1脂肪细胞中脂肪细胞特异性基因表达的维持，包括SCD 1的表达。尽管SCD 2和SCD 1之间的高度序列相似性，但SCD 1的沉默并不下调3 T3-L1细胞分化或基因表达。在给小鼠喂食高脂饮食后，脂肪组织中的SCD 2 mRNA表达也独特地升高了44倍，而SCD 1几乎没有反应。由SCD 2耗竭引起的脂肪形成抑制与过氧化物酶体增殖物激活受体γ（PPAR γ）mRNA和蛋白的减少有关，而在成熟脂肪细胞中，SCD 2的缺失降低了PPAR γ蛋白水平，mRNA水平变化不大。在后一种情况下，SCD 2耗竭未改变PPAR γ蛋白的降解速率，但使用[S-35]甲硫氨酸/半胱氨酸降低了PPAR γ蛋白的代谢标记，表明蛋白翻译降低。在完全分化的脂肪细胞中，SCD 2对最佳蛋白质合成的这种要求通过多核糖体谱分析得到验证，其中响应于SCD 2沉默，mRNA向单体的转变是明显的。这些结果表明，SCD 2是诱导和维持3 T3-L1细胞中的PPAR γ蛋白水平和脂肪形成所必需的。
Based on recent evidence that fatty acid synthase and endogenously produced fatty acid derivatives are required for adipogenesis in 3T3-L1 adipocytes, we conducted a small interfering RNA-based screen to identify other fatty acid-metabolizing enzymes that may mediate this effect. Of 24 enzymes screened, stearoyl-CoA desaturase 2 (SCD2) was found to be uniquely and absolutely required for adipogenesis. Remarkably, SCD2 also controls the maintenance of adipocyte-specific gene expression in fully differentiated 3T3-L1 adipocytes, including the expression of SCD1. Despite the high sequence similarity between SCD2 and SCD1, silencing of SCD1 did not down-regulate 3T3-L1 cell differentiation or gene expression. SCD2 mRNA expression was also uniquely elevated 44-fold in adipose tissue upon feeding mice a high fat diet, whereas SCD1 showed little response. The inhibition of adipogenesis caused by SCD2 depletion was associated with a decrease in peroxisome proliferator-activated receptor gamma ( PPAR gamma) mRNA and protein, whereas in mature adipocytes loss of SCD2 diminished PPAR gamma protein levels, with little change in mRNA levels. In the latter case, SCD2 depletion did not change the degradation rate of PPAR gamma protein but decreased the metabolic labeling of PPAR gamma protein using [S-35] methionine/cysteine, indicating protein translation was decreased. This requirement of SCD2 for optimal protein synthesis in fully differentiated adipocytes was verified by polysome profile analysis, where a shift in the mRNA to monosomes was apparent in response to SCD2 silencing. These results reveal that SCD2 is required for the induction and maintenance of PPAR gamma protein levels and adipogenesis in 3T3-L1 cells.