Inhibition of monoacylglycerol lipase for the treatment of liver disease: tempting but still playing with fire

Lipolytic enzymes have received huge attention due to their crucial role in lipid metabolism and as potential pharmacological targets against obesity and its related disorders. Non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity and today, NAFLD is considered to be the most common chronic liver disorders worldwide.1 The NAFLD pathology covers a wide spectrum of changes, ranging from simple steatosis to non-alcoholic steatohepatitis, progressive fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanisms, particularly those that drive disease progression, are only incompletely understood.1 Central drivers appear to be quantitative and qualitative alterations in lipid metabolic pathways in hepatocytes.1 2 In addition, the impact of altered lipid metabolism in non-parenchymal liver cells and immune cells is increasingly recognised.1 3 Importantly, lipids are stored within the cells and act as signalling molecules or precursors thereof, which further enhances the...

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