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 epidemic disease of public health concern. This spectrum of diseases manifests itself with initial accumulation of excessive triglycerides (due to de novo lipogenesis) in the hepatocytes, leading to simple steatosis. Although its aetiology is multi-factorial, lifestyle changes (diet and physical activity) are considered to be the key thriving factors. In this context, high fructose consumption is associated with an increased risk for developing NAFLD in humans, while high-fructose feeding to experimental animals results in hepatic steatosis and non-alcoholic steatohepatitis, by increasing hepatic lipogenesis. Among several lipogenic genes, the endoplasmic reticulum-bound stearoyl-CoA desaturase 1 (SCD1) is the key determinant of triglycerides biosynthesis pathway, by providing monounsaturated fatty acids, through the incorporation of a double bond at the delta-9 position of saturated fatty acids, specifically, palmitic (C16:0) and stearic (C18:0) acids, yielding palmitoleic (C16:1) and oleic (C18:1) acids, respectively. Various experimental studies involving SCD1 gene knockout and diet-induced rodent models have demonstrated that SCD1 plays a key role in the development of NAFLD, by modulating hepatic lipogenesis and thus triglyceride accumulation in the liver. Several pharmacological and dietary intervention studies have shown the benefits of inhibiting hepatic SCD1 in the pathogenesis of NAFLD. In this review, we give an overview of SCD1 in NAFLD, based on the current experimental evidence and the translational applicability of SCD1 inhibition in human NAFLD conditions, besides discussing the limitations and way-forward.

Keywords: Steatosis, Lipids, Fatty acids, Vitamin A, Metabolic syndrome, Obesity

Core Tip: Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme of biosynthesis of monounsaturated fatty acids that serve as substrates for de novo lipogenesis, thereby increasing the production and accumulation of triglycerides in the liver. The liver-specific inhibition of SCD1 has been shown to attenuate the development of hepatic steatosis and thus non-alcoholic fatty liver disease (NAFLD), as evidenced by experimental studies. The current evidence supports the view that SCD1 is a potential target and the inhibition of this enzyme would certainly help in the control and/or management of NAFLD in humans. However, certain aspects of SCD1 such as its role and regulation need to be addressed in humans to explore its potential translational applicability.