Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2020; 26(25): 3577-3585
Published online Jul 7, 2020. doi: 10.3748/wjg.v26.i25.3577
Monoacylglycerol lipase reprograms lipid precursors signaling in liver disease
Matteo Tardelli
Matteo Tardelli, Division of Gastroenterology and Hepatology, Joan and Sanford I Weill Cornell Department of Medicine, Weill Cornell Medical College, New York, NY 10021, United States
Matteo Tardelli, Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Internal Medicine III, Medical University of Vienna, Vienna 1040, Austria
Author contributions: Tardelli M wrote, ideated, and proofread this manuscript.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
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:
Corresponding author: Matteo Tardelli, MSc, PhD, Lecturer, Postdoctoral Fellow, Division of Gastroenterology and Hepatology, Joan and Sanford I Weill Department of Medicine, Weill Cornell Medical College, 413 E. 69th Street, New York, NY 10021, United States.
Received: March 18, 2020
Peer-review started: March 18, 2020
First decision: May 15, 2020
Revised: June 18, 2020
Accepted: June 23, 2020
Article in press: June 23, 2020
Published online: July 7, 2020

Dietary oversupply of triglycerides represent the hallmark of obesity and connected complications in the liver such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, which eventually progress to cirrhosis and hepatocellular carcinoma. Monoacylglycerol lipase is the last enzymatic step in the hydrolysis of triglycerides, generating glycerol and fatty acids (FAs), which are signaling precursors in physiology and disease. Notably, monoacylglycerol lipase (MGL) also hydrolyzes 2-arachidonoylglycerol, which is a potent ligand within the endocannabinoid system, into arachidonic acid - a precursor for prostaglandin synthesis; thus representing a pivotal substrates provider in multiple organs for several intersecting biological pathways ranging from FA metabolism to inflammation, pain and appetite. MGL inhibition has been shown protective in limiting several liver diseases as FAs may drive hepatocyte injury, fibrogenesis and de- activate immune cells, however the complexity of MGL network system still needs further and deeper understanding. The present review will focus on MGL function and FA partitioning in the horizons of liver disease.

Keywords: Lipid metabolism, Monoacylglycerol lipase, Non-alcoholic steatohepatitis, Non-alcoholic fatty liver disease, Cannabinoid, Nuclear receptors

Core tip: Monoacylglycerol lipase inhibition/modulation is yet unappreciated however attractive therapeutic concept to limit liver disease as fatty acids may drive hepatocyte injury, fibrogenesis and change immune cells phenotype.