Changes in essential fatty acid patterns associated with normal liver regeneration and the progression of hepatocyte nodules in rat hepatocarcinogenesis

Changes in lipid metabolism were monitored in rat hepatocyte nodules at cer tain time points over 9 months. Tissue obtained from partially hepatectomiz ed rats, collected over a period of 7 days, were included as a control for normal hepatocyte cell proliferation. Two important features regarding the lipid profiles of hepatocyte nodules and normal regenerating liver were the increased concentrations of phosphatidylethanolamine (PE), resulting in a decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio, and c holesterol, These changes coincided with increased membrane fluidity in the nodules and regenerating liver. With respect to the fatty acid (FA) profil es of the nodules, C18:1 omega9 and C18:2 omega6 increased in PE and PC whe reas C20:4 omega6 decreased in PC and increased in PE, C22:5 omega6 and C22 :6 omega3, the end products of the omega6 and omega3 metabolic pathways, re spectively, decreased in PC and remained unchanged in PE, The FA levels in PC reflected an impaired delta -6 desaturase enzyme, whereas this effect wa s masked in PE due to the increased concentration of this phospholipid frac tion. In regenerating liver, the FA profiles of PC and PE showed the same p attern as described for the hepatocyte nodules, except for C18:1 omega9 whi ch decreased in PC and increased non-significantly in PE, The increased C18 :1 omega9 level, a FA with anti-oxidative properties, as well as the decrea sed levels of the long-chain polyunsaturated fatty acids (C20 and C22 carbo n chains), have been associated with the decreased lipid peroxidation level in hepatocyte nodules, The resultant decrease in peroxidative metabolites, known to affect apoptosis, could be important in the progression of the no dules into neoplasia, The present results indicate that the altered lipid p arameters associated with hepatocyte nodules closely mimics cellular prolif eration in regenerating liver and could be responsible for the enhanced pro liferation and/or altered growth pattern in these lesions, The altered FA p rofiles suggest various pathways in which FA could play a role in transmemb rane signalling related to the altered cell proliferative and apoptotic pat hways. The persistent changes in the hepatocyte nodules suggest that the li pid metabolism escapes the regulatory mechanisms required for normal cellul ar homeostasis at different levels.