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.
Attie
Alan D
AD
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706-1544, USA. attie@biochem.wisc.edu
Flowers
Matthew T
MT
Flowers
Jessica B
JB
Groen
Albert K
AK
Kuipers
Folkert
F
Ntambi
James M
JM
D000818:Animals; D002779:Cholestasis / Q000209:etiology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D018752:Diet, Fat-Restricted / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology* / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency*
D004040:Dietary Carbohydrates; D004042:Dietary Fats, Unsaturated; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase