Phospholipid metabolism in the liver – Implications for phosphatidylserine in non-alcoholic fatty liver disease

Mammalian cells contain more than a thousand different glycerophospholipid species that are essential membrane components and signalling molecules, with phosphatidylserine (PS) giving membranes their negative surface charge. Depending on the tissue, PS is important in apoptosis, blood clotting, cancer pathogenesis, as well as muscle and brain function, processes that are dependent on the asymmetrical distribution of PS on the plasma membrane and/or the capacity of PS to act as anchorage for various signalling proteins. Recent studies have implicated hepatic PS in the progression of non-alcoholic fatty liver disease (NAFLD), either as beneficial in the context of suppressing hepatic steatosis and fibrosis, or on the other hand as a potential contributor to the progression of liver cancer. This review provides an extensive overview of hepatic phospholipid metabolism, including its biosynthetic pathways, intracellular trafficking and roles in health and disease, further taking a deeper dive into PS metabolism, including associate and causative evidence of the role of PS in advanced liver disease.