Phospholipase A2 controls fatty acid uptake into liver cells in a pharmacologically-responsive way

Excess fat accumulation within the liver leads to non-alcoholic steatohepatitis (NASH)-a serious health threat worldwide. However, the responsible mechanisms and regulation of fatty acid uptake by hepatocytes remain to be uncovered. Using the hepatocyte-derived tumor cell line HepG2, we report that fatty acid influx is mediated by a specific (heterotetrameric) plasma membrane-protein complex constituted of FABPPM, caveolin1, CD36, and phospholipase A2 (iPLA2ß). Within this complex, iPLA2ß serves as a key regulator: iPLA2ß inhibition by the non-toxic bile acid-phospholipid conjugate ursodeoxycholic acid-lysophosp…