Medium-chain phosphatidylcholine (MCPC) as a putative option for suppressing hepatocellular inflammation in cholestatic conditions and steatotic liver diseases

Abstract

The mechanisms of hepatocellular injury in steatotic liver disease (SLD) and cholestasis remain unclear. One hypothesis is that hepatocytes are exposed to unconjugated toxic bile acids due to damage to the biliary mucus layer. Loss of mucus phosphatidylcholine (PC) impairs sealing, allowing unconjugated bile acids secreted in bile to be reabsorbed through leaky biliary epithelium and recirculated via portal blood to hepatocytes (cholehepatic shunting). Augmenting mucus PC could block cholangiocellular uptake of these bile acids and consequent hepatocyte exposure, which is postulated to be achieved through PC supplementation. Medium-chain PC (MCPC), secreted by multidrug resistance protein 3 (MDR3) across the canalicular membrane into bile, does not form micelles with bile acids, thus remaining available to enrich the mucus PC layer. Hepatocellular MCPC for biliary secretion can be increased by direct MCPC delivery or hepatic remodeling of oral long-chain PC provided together with medium-chain triglycerides. The reassembled breakdown products yield MCPC, helping mitigate hepatocellular injury in cholestatic states, including SLD.

Keywords

Cholestasis / phosphatidylcholine / mucus barrier / cholehepatic shunting / unconjugated bile acids / medium-chain phosphatidylcholine

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