NUTRITIONAL INTAKE, ICF-1 LEVEL AND GROWTH FAILURE IN CHOLESTATIC RATS

Abstract

Patients with chronic liver disease have low insulin-like growth factor 1 (IGF-1) levels, but it is not known whether this is secondary to primary hepatic dysfunction and/or to malnutrition. In order to distinguish between these possibilities, serum and liver IGF-1 concentrations and liver IGF-1 mRNA content were compared in three groups of Sprague-Dawley rats; fifteen rats underwent bile duct obstruction (OP); 10 rats were sham-operated and pair-fed with OP rats (PF) to control for nutritional status; and 12 rats were sham-operated controls fed ad libitum (CON). Serum and liver were extracted and assayed by RIA using an antibody that recognizes rat IGF-1 (gift of L.Underwood). Liver ICF-1 mRNA content was measured by dot blot hybridization using a cDNA probe, quantitated by videodensitometry and expressed as a percent of internal control RNA values (adult rat pool). In addition, IGF-1 peptide and mRNA were compared with food intake, nitrogen balance, total weight gain, tail length increase and leg muscle weight. All the parameters were found significantly lower (p<0.001) in OP and PF animals than in CON animals. In the 10 paired OP and PF animals serum and hepatic IGF-1 and liver IGF-1 mRNA Values were not significantly different, despite lower nitrogen balance, tail length gain, and leg muscle weight in the OP animals. For all animals, there was a significant correlation (p<0.001) between serum IGF-1 levels and food intake (r=0.84), liver IGF-1 levels (r=0.64), and liver IGF-1 mRNA (r=0.89). These studies suggest that in chronic bile duct obstruction, the low serum and hepatic IGF-1 levels are primarily due to decreased food intake and appear unrelated to cholestatic liver disease itself. Decreased IGF-1 synthesis is the most probable cause of these low levels. However, factors other than suboptimal nutrition and decreased IGF-1 levels must also contribute to cholestasis-induced growth failure in this animal model.