Lysophospholipid metabolism and signalling in non-alcoholic fatty liver disease

Abstract

Non-alcoholic liver disease (NAFLD) constitutes a global health pandemic. It is estimated that about 25% of the world’s population suffers from NAFLD. In the long-term, a subgroup of the patients can develop inflammation and fibrosis. The end result in some cases is cirrhosis and even liver-related death. The epidemiology and natural history of NAFLD lead to extreme financial costs. To date, there is no approved treatment for NAFLD. Lipotoxicity has been proposed to be one of the main regulators of the implicated molecular pathomechanisms. Research has been focused on the role of cholesterol, free fatty acids and ceramides. Nevertheless, lysophospholipids, such as sphingosine 1-phosphate (S1P), lysophosphatidylcholine (LPC), lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), lysophosphatidylethanolamine (LPE) have emerged as potential contributors to NAFLD/NASH. Finally, the metabolism of other lysophospholipids, such as lysophosphatidylserine (LPSer), lysophosphatidylglycerol (LPG), and lysocardiolipin (LCL), has come to light in the context of NAFLD. In this review, we try to summarize the current knowledge regarding the potential of lysophospholipid signalling and metabolism as therapeutic targets and biomarkers in NAFLD and/or NASH.

Keywords

• non-alcoholic fatty liver disease
• lysophosphatidy