Hepatic amino acid and protein metabolism in non-anorectic, moderately cachectic tumor-bearing rats

Cancer cachexia is characterized by loss of lean body mass. Under this condition peripheral proteins are broken down and transferred to visceral organs and the tumor. The liver is the principal organ in the regulation of protein and amino acid metabolism, but liver amino acid kinetics in cancer are unclear. Therefore, we examined the effects of increasing tumor loads on hepatic protein turnover and amino acid handling.

A MCA-induced sarcoma was implanted subcutaneously 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 acid and L-[3, 4-3H]-valine was given to calculate hepatic substrate fluxes and protein turnover. Serum alpha 2-macroglobulin concentration was measured to determine the acute phase response.

Carcass weight 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 small-tumor-bearing group and 7.3 +/- 0.3 (p < 0.001) in the large-tumor-bearing group, with minimal changes in water content. Serum alpha 2-macroglobulin concentration, essential and gluconeogenic amino acid uptake by the liver increased in large-tumor-bearing animals. This contrasted with reduced liver ammonia uptake and unchanged urea production in tumor-bearing rats. In the small-tumor-bearing group liver protein synthesis increased, whereas protein breakdown remained unchanged. In the large-tumor-bearing group protein synthesis also increased, but protein breakdown decreased to zero.

The study shows that in tumor-bearing rats, liver uptake of essential and gluconeogenic amino acids increases without significant increases in urea or glucose production. Synthesis of both structural and export proteins, e.g. acute phase proteins, increases suggesting that the liver becomes a more efficient nitrogen-sparing and active protein-synthesizing organ during the growth of a malignant tumor.