Influence of glucagon on the synthesis of phosphatidylcholines and phosphatidylethanolamines in monolayer cultures of Rat hepatocytes

Abstract

Diacylglycerols function as common precursors in the biosynthesis of triacylglycerols (TG), phosphatidylcholines (PC) and phosphatidylethanolamines (PE) [ 11. Several investigators have shown that the distribution of diacylglycerols among TG, PC and PE in rat liver can be influenced by varying the dietary state of the animal [2-41. Fasting, for example, causes a drastic inhibition in the formation of hepatic TG 12-71 whereas the synthesis of PC and, particularly, that of PE are much less affected [2-41. These observations suggest that the hormones insulin and glucagon may be involved in the regulation of the biosynthesis of these glycerolipids since the ratio of insulin and glucagon is determined largely by the nutritional state of the animal [8]. In [9] we demonstrated that addition of insulin to monolayer cultures of adult rat hepatocytes [lo] does not alter the rate at which exogenous fatty acids are incorporated into TG, PC and PE. Glucagon also has no effect on the formation of PC and PE from exogenous fatty acids but it causes a marked decrease in the rate of TG synthesis from exogenous fatty acids. Experiments with labelled glucose and glycerol as precursors for the glycerol-backbone of the glycerolipids led also to the suggestion that the increased levels of glucagon occurring in the blood during fasting [ 111, may be important in maintaining the rate of hepatic phospholipid synthesis at the expense of TG synthesis. Several observations [2-41 indicate that the synthesis of PE responds differently to changes in the dietary state than that of PC and that the levels of hepatic PE and PC are differently affected. These observations prompted us to investigate whether glucagon may also exert specific effects on the synthesis of PC and PE. The results suggest that during fasting glucagon may preferentially channel diacylglycerols into PE possibly by increasing the availability of CDPethanolamine.