Stearoyl-CoA Desaturase Deficiency, Hypercholesterolemia, Cholestasis, and Diabetes

Previous studies showed that mice deficient in Scd1 had a reduced level of liver triglyceride and an improvement in insulin sensitivity. We studied Scd1(-/-) mice on a very low-fat, high-carbohydrate lipogenic diet. The animals were almost entirely devoid of high-density lipoprotein (HDL). Nonetheless, they were hypercholesterolemic and had cholestasis. These changes were reversible with oil containing both mono- and polyunsaturated fat, but not entirely reversible with just triolein, suggesting that Scd1 deficiency increased the requirement for polyunsaturated fat. We also found that the Scd1(-/-) mice on a normal chow diet had dramatically improved insulin sensitivity. However, leptin(ob/ob) Scd1(-/-) mice had worse diabetes than leptin(ob/ob) Scd1(wt/wt) mice.