Scd1 Knockout Mice on very low fat diet. Mus musculus

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) Overall design: 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.