Transcription profiling by array of SCD1 knock-out mice

Stearoyl-CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1-/- mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1-/- mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage. Experiment Overall Design: RNA was isolated from livers of 10 individual 6-week-old female mice by using a standard method. Mouse genome U74A arrays were used to monitor the expression level of approximately 10,000 genes and expressed sequence tags (Affymetrix). Genes differentially expressed were identified by comparing expression levels in SCD1-/- and wild-type mice.硬脂酰辅酶A去饱和酶（Stearoyl-CoA desaturase, SCD）是核心脂肪生成酶，可催化单不饱和脂肪酸的合成，主要为油酸酯（C18:1）与棕榈油酸酯（C16:1），这两种物质均为膜磷脂、甘油三酯、蜡酯及胆固醇酯的组成成分。小鼠体内存在SCD1~SCD3共3种SCD同工型。本研究证实，SCD1同工型靶向敲除的小鼠体脂含量降低、胰岛素敏感性增强，且可抵御饮食诱导的体重增长。该抗肥胖效应伴随能量消耗提升与耗氧量增加。与野生型小鼠相比，SCD1敲除（SCD1-/-）小鼠的血浆酮体水平升高，而血浆胰岛素与瘦素水平降低。在SCD1-/-小鼠体内，多个脂质氧化相关基因的表达水平上调，而脂质合成相关基因的表达水平则出现下调。上述研究结果表明，SCD1缺失除了会减少甘油三酯的合成与储存外，还可激活脂质氧化过程。实验整体设计：采用标准方法从10只6周龄雌性小鼠的肝脏中提取总RNA。使用小鼠基因组U74A芯片（Affymetrix）对约10000个基因及表达序列标签（expressed sequence tags）的表达水平进行检测。通过对比SCD1敲除（SCD1-/-）与野生型小鼠的基因表达水平，鉴定得到差异表达基因。