Stearoyl-CoA desaturase: A novel control point of lipid metabolism and insulin sensitivity

Abstract

Stearoyl-CoA desaturase (SCD) is a central enzyme responsible for the synthesis of monounsaturated fatty acids – mainly oleate. Recent studies have shown that SCD1 plays also a significant role in the regulation of lipid metabolism. SCD1-deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin-mediated weight loss, and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice and attenuates fasting-induced liver steatosis in PPARα-deficient mice. Lack of SCD1 expression also improves insulin action in skeletal muscles and prevents diet-induced hepatic insulin resistance in mice. Much evidence indicates that the direct anti-steatotic and anti-diabetic effects of SCD1 deficiency stem from the decreased tissue lipid content caused by enhanced fatty acid oxidation and reduced lipid synthesis. In this review, we discuss our current understanding of the role of SCD1 in insulin resistance and regulation of hepatic lipid partitioning, and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of non-alcoholic fatty liver disease and in the prevention of diabetes.