Monoacylglycerol lipase reprograms lipid precursors signaling in liver disease

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.