Submitted on October 22, 2007
Accepted on October 23, 2007
Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice
Marcia L.E. MacDonald, Roshni R. Singaraja, Nagat Bissada, Piers Ruddle, Russell Watts, Joanna M. Karasinska, William T. Gibson, Catherine Fievet, Jean E. Vance, Bart Staels, and Michael R. Hayden
Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4
Corresponding Author: mrh{at}cmmt.ubc.ca
A combination of the interrelated metabolic risk factors obesity, insulin resistance, dyslipidemia and hypertension, often described as “metabolic syndrome”, is known to increase the risk of developing cardiovascular disease and diabetes. Stearoyl-CoA desaturase (SCD) activity has been implicated in the metabolic syndrome, but detailed studies on 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 LXR agonists. Our results demonstrate that constitutive reduction of SCD activity improves the metabolic phenotype of the LDLR-deficient mice on a western diet.
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