title: Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice.
abstract: A combination of the interrelated metabolic risk factors obesity, insulin resistance, dyslipidemia, and hypertension, often described as the "metabolic syndrome," is known to increase the risk of developing cardiovascular disease and diabetes. Stearoyl-coenzyme A desaturase (SCD) activity has been implicated in the metabolic syndrome, but detailed studies of the beneficial metabolic effects of SCD deficiency have been limited. Here, we show that absence of the Scd1 gene product reduces plasma triglycerides and reduces weight gain in severely hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a Western diet. Absence of SCD1 also increases insulin sensitivity, as measured by intraperitoneal glucose and insulin tolerance testing. SCD1 deficiency dramatically reduces hepatic lipid accumulation while causing more modest reductions in plasma apolipoproteins, suggesting that in conditions of sustained hyperlipidemia, SCD1 functions primarily to mediate lipid stores. In addition, absence of SCD1 partially ameliorates the undesirable hypertriglyceridemic effect of antiatherogenic liver X receptor agonists. Our results demonstrate that constitutive reduction of SCD activity improves the metabolic phenotype of LDLR-deficient mice on a Western diet.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Marcia L E
authors.initials: ML
authors.lastname: MacDonald
authors.forename: Roshni R
authors.initials: RR
authors.lastname: Singaraja
authors.forename: Nagat
authors.initials: N
authors.lastname: Bissada
authors.forename: Piers
authors.initials: P
authors.lastname: Ruddle
authors.forename: Russell
authors.initials: R
authors.lastname: Watts
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Karasinska
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
authors.forename: Catherine
authors.initials: C
authors.lastname: Fievet
authors.forename: Jean E
authors.initials: JE
authors.lastname: Vance
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D050154:Adiposity / Q000502:physiology; D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D004032:Diet / Q000009:adverse effects; D005234:Fatty Liver / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D008055:Lipids; D011973:Receptors, LDL; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase