Role of metabolic overload in the initiation of DNA synthesis following partial hepatectomy in the rat

Abstract

Changes in hepatic ATP energy charge (EC = ATP +0.5 ADP/ATP + ADP AMP) as an expression of metabolic overload and oxidative phosphorylation were studied conjointly with DNA synthesis after partial hepatectomy (PH) in the male rat. ATP and EC showed a significant decrease while mitochondrial phosphorylative activity was enhanced within 24 h. Confronted with the pattern of DNA synthesis, the above changes were clearly separated in time from the actual process of DNA synthesis. Fasting delayed the recovery of EC as well as the peak value in the rate of thymidine incorporation. Extended glucose infusion prevented the drop of ATP during the entire period of treatment and considerably reduced fat infiltration and glycogen breakdown. In these glucose-infused rats, unchanged blood sugar was associated with tendency for plasma insulin to rise and suppression of the usual posthepatectomy hyperglucagonemia. With these metabolic and hormonal changes, an important delay in the onset and modification of the whole pattern of DNA synthesis were observed. The latter process began consistently only after a late fall of ATP which followed the cessation of glucose infusion. It is suggested that changes in energy metabolism, taken as an expression of hepatocyte metabolic overload following PH, account for the early events involved in the initiation of DNA synthesis, and probably regulate hepatocyte response to systemic hepatotrophic factors.