Energy metabolism and regeneration in transgenic mouse liver expressing creatine kinase after major hepatectomy

Background & Aims: The catalysis of a creatine/phosphocreatine system by creatine kinase is not expressed in the liver. The aim of this study was to examine energy metabolism and regeneration after hepatectomy using transgenic mouse liver expressing creatine kinase to clarify the effects of phosphocreatine on liver regeneration. Methods: Transgenic mice were divided into two groups: group 1 was fed normal chow, and group 2 was fed 10% creatine chow for 5 days. Hepatic energy metabolism was evaluated before and after hepatectomies. Changes in remnant liver weight gain and bromodeoxyuridine labeling index were measured after 70% and 80% hepatectomies. Results: Hepatic adenosine triphosphate level 24 hours after 70% hepatectomy was significantly higher in group 2 than group 1 (P < 0.05). In group 2, mitochondrial adenosine triphosphate synthesis was enhanced because of elevated intramitochondrial adenine nucleotide content before hepatectomy, leading to sufficient adenosine triphosphate synthesis after a 70% hepatectomy. Bromodeoxyuridine DNA labeling index 24 hours after a 70% hepatectomy was significantly higher in group 2 than group 1. Rapid liver weight gain was observed in group 2 after a 70% hepatectomy, Conclusions: Abundant phosphocreatine promotes liver regeneration by reinforced hepatic energy metabolism. Gene transfer of creatine kinase to the liver may be a potential method in liver surgery.