HEPATIC AMINO-ACID AND PROTEIN-METABOLISM IN NON-ANORECTIC, MODERATELY CACHECTIC TUMOR-BEARING RATS

Background/Aims: Cancer cachexia is characterized by loss of lean body mass. Under this condition peripheral proteins are broken down and tr ansferred to visceral organs and the tumor. The liver is the principal organ in the regulation of protein and amino acid metabolism, but liv er amino acid kinetics in cancer are unclear. Therefore, we examined t he effects of increasing tumor loads on hepatic protein turnover and a mino acid handling. Methods: A MCA-induced sarcoma was implanted subcu taneously in Lewis rats (200-225 g). Rats were studied when the tumor was 5-15% or 15-30% of body weight. Control rats were sham implanted. Under anesthesia, a primed constant infusion of para-aminohippuric aci d and L-[3, 4-H-3]-valine was given to calculate hepatic substrate flu xes and protein turnover. Serum alpha(2)-macroglobulin concentration w as measured to determine the acute phase response. Results: Carcass we ight decreased approximately 10% in large-tumor-bearing rats (p<0.001) . Liver wet weight increased from 5.5+/-0.1 (g) to 5.9+/-0.2 in the sm all-tumor-bearing group and 7.3+/-0.3 (p<0.001) in the large-tumor-bea ring group, with minimal changes in water content. Serum alpha(2)-macr oglobulin concentration, essential and gluconeogenic amino acid uptake by the liver increased in large-tumor-bearing animals. This contraste d with reduced liver ammonia uptake and unchanged urea production in t umor-bearing rats. In the small-tumor-bearing group liver protein synt hesis increased, whereas protein breakdown remained unchanged. In the large-tumor-bearing group protein synthesis also increased, but protei n breakdown decreased to zero. Conclusions: The study shows that in tu mor-bearing rats, liver uptake of essential and gluconeogenic amino ac ids increases without significant increases in urea or glucose product ion. Synthesis of both structural and export proteins, e.g. acute phas e proteins, increases suggesting that the liver becomes a more efficie nt nitrogen-sparing and active protein-synthesizing organ during the g rowth of a malignant tumor.