Age-Related Variations in Hepatic Biosynthesis of Phosphatidylcholine: A Study of Choline Metabolism with Perfused Rat Liver

Abstract

This study investigated the age-related increase in phospholipid secretion previously described in perfused rat livers. The hypothesis of this study was that the increased secretion is mainly due to an enhanced hepatic biosynthesis of phosphatidylcholine (PC). Specifically, we evaluated the contribution to this increase of the major hepatic pathway of phosphatidylcholine formation (i.e., the conversion of choline into phosphatidylcholine via cytidine diphosphate [CDP]-choline). The measurements of [3H]choline incorporation into phosphatidylcholine and its precursors in liver and bile throughout the 2-hr duration of the experiments showed significant differences in the amount of newly synthesized labeled PC secreted in the bile produced by adult and young rat livers. However, the present findings do not support the idea that the age-related increase in phosphatidylcholine hepatic secretion was due only to a strong increase in phosphatidylcholine synthesis by via CDP-choline. Conversely, they suggest that future research should be directed towards the mechanisms regulating the diacylglycerol metabolism in the hepatocytes, as the alteration of the splitting ratio of hepatic diacylglycerol flow could lead to an age-related increase in conversion of diacylglycerol into phosphatidylcholine, rather than into triacylglycerol. This, in turn, may decrease the availability of triacylglycerol for hepatic very low density lipoprotein (VLDL) assembly and contribute to altered VLDL synthesis, as previously observed in the aging process.