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World J Hepatol. Jan 27, 2022; 14(1): 168-179
Published online Jan 27, 2022. doi: 10.4254/wjh.v14.i1.168
Stearoyl-CoA desaturase 1: A potential target for non-alcoholic fatty liver disease?-perspective on emerging experimental evidence
Shanmugam Murugaiha Jeyakumar, Ayyalasomayajula Vajreswari
Shanmugam Murugaiha Jeyakumar, Ayyalasomayajula Vajreswari, Division of Lipid Biochemistry, National Institute of Nutrition, Hyderabad 500007, Telangana, India
Shanmugam Murugaiha Jeyakumar, Department of Clinical Pharmacology, National Institute for Research in Tuberculosis, Chennai 600031, Tamil Nadu, India
Author contributions: Jeyakumar SM contributed to conception, summary art drawing, and drafting, reviewing, and finalization of the manuscript; Vajreswari A contributed to critical reviewing of the manuscript.
Supported by Indian Council of Medical Research (ICMR), No. 5/4/3-10/TF/2011/NCD-II; Department of Biotechnology (DBT), No. BT/PR6145/FNS/20/566/2012; and ICMR-NIN-Intramural Grant.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shanmugam Murugaiha Jeyakumar, PhD, Senior Scientist, Department of Clinical Pharmacology, National Institute for Research in Tuberculosis, No. 1 Mayor Sathiyamoorthy Road, Chetpet, Chennai 600031, Tamil Nadu, India. smjkumar@gmail.com
Received: May 3, 2021
Peer-review started: May 3, 2021
First decision: June 15, 2021
Revised: June 18, 2021
Accepted: December 10, 2021
Article in press: December 10, 2021
Published online: January 27, 2022
Processing time: 262 Days and 21.6 Hours
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.