Stearoyl-CoA desaturase 1: A potential target for non-alcoholic fatty liver disease?-perspective on emerging experimental evidence

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease and one of the leading causes of death. An unnamed disease has become a global epidemicdisease of public health concern. This spectrum of diseases manifests itself withinitial accumulation of excessive triglycerides (due to de novo lipogenesis) in thehepatocytes, leading to simple steatosis. Although its aetiology is multi-factorial,lifestyle changes (diet and physical activity) are considered to be the key thrivingfactors. In this context, high fructose consumption is associated with an increasedrisk for developing NAFLD in humans, while high-fructose feeding to experimentalanimals results in hepatic steatosis and non-alcoholic steatohepatitis, byincreasing hepatic lipogenesis. Among several lipogenic genes, the endoplasmicreticulum-bound stearoyl-CoA desaturase 1 (SCD1) is the key determinant oftriglycerides biosynthesis pathway, by providing monounsaturated fatty acids,through the incorporation of a double bond at the delta-9 position of saturatedfatty acids, specifically, palmitic (C16:0) and stearic (C18:0) acids, yieldingpalmitoleic (C16:1) and oleic (C18:1) acids, respectively. Various experimentalstudies involving SCD1 gene knockout and diet-induced rodent models havedemonstrated that SCD1 plays a key role in the development of NAFLD, bymodulating hepatic lipogenesis and thus triglyceride accumulation in the liver.Several pharmacological and dietary intervention studies have shown the benefitsof inhibiting hepatic SCD1 in the pathogenesis of NAFLD. In this review, we givean overview of SCD1 in NAFLD, based on the current experimental evidence andthe translational applicability of SCD1 inhibition in human NAFLD conditions,besides discussing the limitations and way-forward