Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism

Stearoyl-coenzyme A desaturase 1 (SCD1) is a central regulator of fuel metabolism and may represent a therapeutic target to control obesity and the progression of related metabolic diseases including type 2 diabetes and hepatic steatosis. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate and palmitoleate, which are important in controlling weight gain in response to feeding high carbohydrate diets. In this review, we evaluate the role of SCD1 isoform in the regulation of lipid and glucose metabolism in metabolic tissues. These highlights of recent findings are aimed toward advancing our understanding of the role of SCD1 in the development of metabolic diseases, which may help evaluate the possible health outcomes of modulating MUFA levels through targeting SCD1 activity. SCD1 tissue-specific deficiency in liver and skin protects against HCD and HFD, respectively, indicating that SCD1 carries out distinct metabolic functions in different tissues. SCD1 products, oleate and palmitoleate, have different metabolic properties. Palmitoleate reduces hepatic lipogenesis and improves insulin sensitivity, while oleate promotes ectopic fat accumulation and increases glucose intolerance. Reduced SCD1 activity in the liver caused ER stress that was only normalized by exogenous or endogenous oleate but not palmitoleate. Hepatic oleate, but not palmitoleate, regulates body weight. Exercise increases SCD1 activity in skeletal muscle, indicating increased FA synthesis, and was proposed to be protective against weight gain. SCD1 deficiency-mediated glucose uptake in skeletal muscle and BAT feeds toward glycogen synthesis. Hepatic oleate modulates FA synthesis and oxidation in WAT. Localized and systemic SCD1 deficiency increases glucose uptake in WAT through apparently different mechanisms involving GLUT1 and GLUT4, respectively.