Journal of Lipid Research
Volume 47, Issue 12, December 2006, Pages 2668-2680
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Research Article
Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diets⃞

https://doi.org/10.1194/jlr.M600203-JLR200Get rights and content
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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−/− 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.

monounsaturated fatty acids
polyunsaturated fatty acids
lipoprotein X
very low density lipoprotein
high density lipoprotein
apolipoprotein B
apolipoprotein A-I
stearoyl-coenzyme A desaturase 1
essential fatty acid
bile acids

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Published, JLR Papers in Press, September 28, 2006.

Abbreviations:

    apoB

    apolipoprotein B

    FPLC

    fast-protein liquid chromatography

    IDL

    intermediate density lipoprotein

    SCD1

    stearoyl-coenzyme A desaturase 1

    SREBP-1c

    sterol-regulatory element binding protein-1c

    VLF

    very low-fat

s⃞

The online version of this article (available at http://www.jlr.org) contains supplemental data in the form of 4 tables and 2 figures.