Scd1 Knockout Mice on very low fat diet

Stearoyl-CoA desaturase 1-deficient (SCD1-/-) mice have impaired monounsaturated fatty acid (MUFA) synthesis. When maintained on a very low-fat, high-carbohydrate (VLF-HC) diet, SCD1-/- mice develop severe hypercholesterolemia characterized by an increase in apolipoprotein B-containing lipoproteins and the appearance of lipoprotein-X. Additionally, high-density lipoprotein cholesterol is dramatically reduced in VLF-HC SCD1-/- mice. The concomitant presence of elevated plasma bile acids, bilirubin and aminotransferases in the VLF-HC SCD1-/- mouse are indicative of hepatic dysfunction. Supplementation of the VLF-HC diet with unsaturated fat (canola oil), but not saturated fat (coconut oil), prevents these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing low-density lipoprotein cholesterol, signifying an additional role for dietary polyunsaturated fatty acid deficiency in the development of this phenotype. These results indicate that lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Keywords: repeat (genotype and diet) We used Affymetrix Mouse430v2.0 microarray chips to search for gene expression changes unique to the VLF-HC SCD1-/- group. These chips contain 45,101 probe sets representing over 39,000 transcripts and variants from over 34,000 mouse genes. We studied SCD1+/+ and SCD1-/- mice on chow or the VLF-HC diet, analyzing five individual livers from each subgroup for a total of twenty microarrays.

硬脂酰辅酶A去饱和酶1缺陷（Stearoyl-CoA desaturase 1-deficient, SCD1-/-）小鼠的单不饱和脂肪酸（monounsaturated fatty acid, MUFA）合成能力受损。当饲养于极低脂高糖（very low-fat, high-carbohydrate, VLF-HC）饲料时，SCD1-/-小鼠会出现严重高胆固醇血症，其特征为含载脂蛋白B（apolipoprotein B, apoB）的脂蛋白水平升高，并出现脂蛋白-X（lipoprotein-X）。此外，VLF-HC饲料饲养的SCD1-/-小鼠体内高密度脂蛋白胆固醇（high-density lipoprotein cholesterol, HDL-C）水平显著降低。VLF-HC饲料饲养的SCD1-/-小鼠血浆中胆汁酸、胆红素及氨基转移酶水平同时升高，这一表现提示存在肝功能异常。在VLF-HC饲料中补充不饱和脂肪（菜籽油，canola oil）而非饱和脂肪（椰子油，coconut oil），可预防上述血浆表型的出现。然而，膳食油酸（oleate）在降低低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）方面的效果不及菜籽油，这表明膳食多不饱和脂肪酸（polyunsaturated fatty acid, PUFA）缺乏在该表型的发生发展中发挥了额外作用。上述结果表明，SCD1缺失会使小鼠对膳食不饱和脂肪的需求增加，以弥补单不饱和脂肪酸合成受损，并预防高胆固醇血症与肝功能异常。
关键词：重复（基因型与饮食）
我们采用Affymetrix Mouse430v2.0基因芯片，以筛选VLF-HC饲养的SCD1-/-组特有的基因表达变化。该芯片包含45101个探针组，可代表超过34000个小鼠基因的39000余种转录本及变异体。我们对饲喂常规饲料或VLF-HC饲料的SCD1+/+与SCD1-/-小鼠进行研究，每个亚组取5个独立肝脏样本进行分析，总计完成20次基因芯片检测。