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

Abstract

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.

Figure 1. Hepatic oleate regulates FA metabolism in adipose tissues

(A) In SCD1 GKO mice, reduced hepatic oleate synthesis reduces liver triglycerides accumulation and decreases plasma oleate. Reduced plasma oleate enhances lipogenesis and FA oxidation in white adipose tissue which subsequently decrease adipose tissue fat mass. Hepatic oleate is transported to adipose tissue in very low density lipoprotein in the form of TG and CE. (B) Global SCD1 deletion induced changes are suppressed upon hepatic oleate restoration through human SCD5 overexpression in the liver of SCD1 GKO mice. Also, restored hepatic oleate increased fat accumulation in the liver. SCD1 GKO (SCD1 global knockout) mice

Figure 2. SCD1 deficiency induces ER stress

Despite preferred phenotypes observed in SCD1 deficient mice, SCD1 deficiency is associated with ER stress which seems independent of reduced body weight and hypoglycemia observed in these mice.