Interorgan glutamine metabolism in the tumor-bearing rat

Abstract

The effects of progressive malignant disease on gut/liver glutamine metabolism were studied in order to gain further insight into the altered glutamine metabolism that characterizes the host with cancer and to further elucidate the causes and consequences of glutamine depletion in tumor-bearing rats. Rats were inoculated on Day 0 with 2 × 10 6 viable fibrosarcoma cells and blood glutamine was measured every 6 days. On Day 24 the animals underwent laparotomy and sampling of arterial, portal venous, and hepatic venous blood. Arterial glutamine fell by more than one-third in tumor-bearing rats and the arterial-portal venous concentration difference for glutamine across the intestinal tract was diminished by 50% ( P < 0.01). Simultaneously the fractional extraction of glutamine by the gut was reduced from 21 to 15% ( P < 0.05). The liver switched from an organ of near glutamine balance in control rats to one of marked glutamine output in tumor-bearing rats ( P < 0.01). The wet weight of the small intestine was diminished by 15% in tumor-bearing rats and villous height was uniformly decreased in tumor-bearing rats with an average reduction in villous height of 26% ( P < 0.05). The causes of glutamine depletion in this tumor-bearing rat model remain unclear. The growing tumor may behave as a glutamine trap but also appears to alter glutamine metabolism in vital metabolic processing centers such as the gut and liver. Malignant cells may compete with gut mucosal cells for glutamine resulting in a diminished gut glutamine utilization and detrimental changes in mucosal architecture. The altered glutamine metabolism that characterizes these tumor-bearing rats may be one component of cancer cachexia.