Increase in diacylglycerol production by liver and liver cell nuclei at old age

Early experiments have shown that sustained elevation of diacylglycerol (DAG) level in liver cell plasma membranes of aged rats is an essential prerequisite for disturbances in agonist responsiveness of hepatocytes. However, the mechanisms responsible for the age-related rise in DAG content in liver cells have not been clearly identified. The aim of the present study was to determine if phospholipid degradation by endogenous phospholipases precedes the DAG accumulation in liver cells and cell nuclei. The DAG formation in liver slices, hepatocytes and liver cell nuclei has been studied in 90-and 720-day-old rats. The experiments were performed in either the [C-14]CH3COOH-labeled rat liver or liver slices, or hepatocytes pre-labeled by [C-14] linoleic or [C-14] oleic or/and [H-3] arachidonic acid. The metabolism of C-14-linoleil]phosphatidylcholine (PC) and [C-14-methyl] PC was investigated in isolated liver cell nuclei. The [C-14]DAG production in pre-labeled liver slices and in hepatocytes increased significantly and [C-14] phosphatidylethanol formation decreased with age. DAG formed in liver of old animals showed labeling ratios (C-14/H-3) close to those of PC, pointing to PC as the primary DAG source in senescent liver. The liver slices of old rats, pre-labeled in situ by [C-14]CH3COOH, demonstrated the enhanced ability to produce DAG and sphingomyelin (SM) in a time-dependent manner while the PC level decreased in liver of old rats. The production of [C-14]DAG, [C-14]SM and [C-14] phosphocholine in the nuclei of old rats was significantly higher than that in adult animals. These results suggest that PLC and SM synthase activities play a key role in a regulation of DAG basal levels present in the liver cells and in the nuclei of old rats. (C) 2002 Elsevier Science Inc. All rights reserved.