Liver regeneration : With reference to malnutrition and growth factors

Sammanfattning: The liver has a unique capacity to regenerate after damage, irrespective of cause. The regulatory mechanisms of this regeneration are not fully known. Liver regeneration· is associated with rapid growth and thereby increased demands for energy and synthesis of new compounds. These studies were undertaken to evaluate the impact of malnutrition on liver regeneration, to observe the consequences for energy metabolism and protein synthesis, and to investigate the potential effects of some growth factors and cholecystokinin on liver regeneration.Liver regeneration was studied in rats after 70 % liver resection. Malnutrition was induced by feeding with only 25 % of normal intake for one week. The regeneration rate was measured from incorporation of continuously infused radiolabelled thymidine and from liver DNA content and liver weight. Liver composition and contents of energy-rich substrateswere studied before and after regeneration. Protein synthesis was determined with a flooding dose method using labelled phenylalanine. The concentrations of epidermal growth factor (EGF), transfornting growth factor alpha (TGF-a) and insulin-like growth factor I (IGF-1) were measured in plasma and liver tissue. A constant endogenous increase in plasma cholecystokinin was induced by surgical pancreaticobiliary diversion.The studies showed that in malnourished rats the regeneration rate of hepatocytes was reduced and the rate of gain in liver weight, DNA and protein content decreased when expressed as absolute values. After 48 hours of regeneration, fat and water content had increased and glycogen and protein concentration decreased. Malnutrition was associated with a decrease in energy-rich phosphates and energy charge potential in the liver, but during regeneration in the malnourished state liver energy metabolism was given priority, with values rising to at least the same level as in the well-nourished group. Protein synthesis was stimulated during liver regeneration. After 48 hours of regeneration protein synthesis was greater in well-nourished than in malnourished rats. EGF concentrations were elevated in both plasma and liver tissue after 48 hours of liver regeneration indicating a role of EGF in that process. Levels of TGF-a were not then changed, suggesting that it is not important at this stage of regeneration. IGF-I concentrations were increased in regenerating hepatic tissue, implying a possible effect on regeneration. Malnutrition per se increased the plasma EGF levels, indicating involvement in the body's defense against malnutrition. Pancreaticobiliary diversion associated with increased cholecystokinin levels induced pancreatic hypertrophy and hyperplasia but no change was seen in the rate of liver regeneration.