A role for high density lipoproteins in hepatic phosphatidylcholine homeostasis

Choline is (95%) found largely in the biosphere as a component of phosphatidylcholine (PC) which is made from choline via the CDP-choline pathway. Animals obtain choline from both the diet and via endogenous biosynthesis that involves the conversion of phosphatidylethanolamine into PC by phosphatidylethanolamine N-methyltransferase (PEMT), followed by PC catabolism. We have uncovered a striking gender-specific conservation of choline in female mice that does not occur in male mice. Female Pemt−/− mice maintained hepatic PC/total choline levels during the first day of choline deprivation and escaped liver damage whereas male Pemt−/− mice did not. Plasma PC levels in high-density lipoproteins (HDLs) were higher in male Pemt−/− mice than those in females before choline deprivation. Interestingly, after choline deprivation for 1 day, female, but not male, Pemt−/− mice increased HDL-PC levels. Glybenclamide, an inhibitor of PC efflux mediated by ABC transporters, eliminated this response to choline deprivation in females. These data suggest that (i) increased PC efflux from extra-hepatic tissues to HDLs in the circulation provided sufficient choline for the liver and compensated for loss of hepatic PC during the initial stages of choline deprivation in female, but not male, Pemt−/− mice, and (ii) plasma HDL in female mice has an important function in maintenance of hepatic PC as an acute response to severe choline deprivation.