Hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survival after partial hepatectomy in mice

Abstract

A major predictor of failed liver resection and transplantation is nonalcoholic fatty liver disease (NAFLD). NAFLD is linked to a wide spectrum of diseases including obesity and diabetes that are increasingly prevalent in Western populations. Thus, it is important to develop therapies aimed at improving posthepatectomy outcomes in patients with NAFLD, as well as to improve the evaluation of patients slated for hepatic surgery. Decreased hepatic phosphatidylcholine (PC) content and decreased ratio of hepatic PC to phosphatidylethanolamine (PE) have previously been linked to NAFLD. To determine if decreased hepatic PC/PE could predict survival after hepatectomy, we used mouse models lacking key enzymes in PC biosynthesis, namely, phosphatidylethanolamine N-methyltransferase and hepatic-specific CTP:phosphocholine cytidylyltransferase α. These mice were fed a high-fat diet to induce NAFLD. We then performed a 70% partial hepatectomy and monitored postoperative survival. We identified hepatic PC/PE to be inversely correlated with the development of steatosis and inflammation in the progression of NAFLD. Decreased hepatic PC/PE before surgery was also strongly associated with decreased rates of survival after partial hepatectomy. Choline supplementation to the diet increased hepatic PC/PE in Pemt(-/-) mice with NAFLD, decreased inflammation, and increased the survival rate after partial hepatectomy.

Conclusion: Decreased hepatic PC/PE is a predictor of NAFLD and survival following partial hepatectomy. Choline supplementation may serve as a potential therapy to prevent the progression of NAFLD and to improve postoperative outcome after liver surgery.