Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet
Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet
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DOI：
10.1194/jlr.m600203-jlr200
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发表时间：
2006-12-01
影响因子：
6.5
通讯作者：
Attie, Alan D.
中科院分区：
文献类型：
--
作者：
Flowers, Matthew T.;Groen, Albert K.;Attie, Alan D.
硬脂酰辅酶A去饱和酶1缺陷（SCD1(-/-)）小鼠的MUFA合成受损。当维持极低脂（VLF）饮食时，SCD1（-/-）小鼠出现严重的高胆固醇血症，其特征是含载脂蛋白B （apoB）的脂蛋白增加和脂蛋白x的出现。与VLF SCD1（-/-）小鼠相比，VLF SCD1（-/-）小鼠的LDL清除率降低，表明含载脂蛋白B的脂蛋白清除率降低导致了高胆固醇血症。此外，这些小鼠体内的高密度脂蛋白胆固醇也显著降低。VLF SCD1(-/-) 2小鼠血浆胆汁酸、胆红素和转氨酶升高提示胆汁淤积。在VLF饮食中添加富含MUFA和pufa的菜籽油，而不是富含饱和脂肪的氢化椰子油，可以防止这些血浆表型。然而，饮食中的油酸在降低低密度脂蛋白胆固醇方面不如菜籽油有效，这表明饮食中PUFA缺乏在这种表型的发展中起作用。这些结果表明，缺乏SCD1会导致饮食中不饱和脂肪的需求增加，以补偿MUFA合成受损，并防止高胆固醇血症和肝功能障碍。因此，在膳食不饱和脂肪不足的情况下，内源性多聚脂肪酸的合成是必不可少的，并影响多聚脂肪酸的膳食需求。
Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of lipoprotein X. The rate of LDL clearance was decreased in VLF SCD1(-/-) mice relative to VLF SCD1(-/-) mice, indicating that reduced apoB-containing lipoprotein clearance contributed to the hypercholesterolemia. Additionally, HDL-cholesterol was dramatically reduced in these mice. The presence of increased plasma bile acids, bilirubin, and aminotransferases in the VLF SCD1(-/-) 2 mice is indicative of cholestasis. Supplementation of the VLF diet with MUFA- and PUFA-rich canola oil, but not saturated fat-rich hydrogenated coconut oil, prevented these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing LDL-cholesterol, signifying a role for dietary PUFA deficiency in the development of this phenotype. These results indicate that the 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. Therefore, endogenous MUFA synthesis is essential during dietary unsaturated fat insufficiency and influences the dietary requirement of PUFA.