Medium-Chain Phosphatidylcholine (MCPC) as a Hypothetical Option for Suppressing Hepatocellular Inflammation in Cholestatic Conditions and Fatty Liver Diseases

The development of hepatocellular injury in cholestatic conditions is not well understood. It has been suggested that exposure of hepatocytes to toxic unconjugated bile acids may trigger this process. In cholestasis, damage to the mucus layer covering the biliary mucosa is postulated. A consequential lack of mucus phosphatidylcholine impairs the sealing capacity towards bile. Thus, after being secreted into bile, toxic unconjugated bile acids can be reabsorbed through the leaky biliary epithelium and recirculated via portal blood to hepatocytes in a process known as cholehepatic shunting. Increasing the phosphatidylcholine content of the mucus could prevent the uptake of these toxic bile acids by cholangiocytes, thereby preventing their subsequent exposure to hepatocytes. This can be achieved by supplementing the mucus with phosphatidylcholine. Medium-chain phosphatidylcholine (MCPC), which is secreted by MDR3 across the canalicular plasma membrane of hepatocytes and appears in bile, does not associate with bile acids to form micelles. Therefore, it remains available to enhance the mucus phosphatidylcholine layer. There are two ways to increase the hepatocellular concentration of MCPC in hepatocytes for secretion in bile: MCPC can be provided directly, or the metabolic capacity of hepatocytes can be utilized to remodel MCPC from orally administered long-chain phosphatidylcholine alongside the simultaneous provision of medium-chain triglycerides. In the latter case, the breakdown products of these substances combine to form MCPC within hepatocytes, which are then secreted in bile.