Dietary regulation of the hepatic system n glutamine transporter in tumor-bearing rats.
BACKGROUND
Hepatocytes possess a novel, plasma-membrane, sodium ion (Na+)-independent, glutamine transporter (system n), which functions to transport glutamine out of the cell into the blood. In the tumor-bearing rat, the activity of system n increases but its regulation is unknown. We hypothesized that the increase in system n that occurs in rats with cancer was related to a fall in the circulating glutamine concentration.


METHODS
Ten male rats underwent flank implantation with a cube of methylcholanthrene-induced fibrosarcoma cells and 10 rats underwent a sham operation. After 9 days of standard diet, all rats were randomized to receive either a glutamine-enriched oral diet or an isonitrogenous diet without supplemental glutamine, for 1 week. Tumors and livers were harvested 16 days postimplantation. Arterial blood samples were obtained from all animals. Hepatic plasma membrane vesicles were prepared and the carrier-mediated, Na(+)-independent transport of glutamine was assayed.


RESULTS
When compared to nontumor-bearing animals, tumor-bearing rats that were fed a control diet exhibited hypoglutaminemia and a 2.3-fold increase in the activity of system n. Glutamine dietary supplementation produced blood glutamine levels that were similar in both tumor-bearing and nontumor-bearing rats, apparently abrogating the increase in system n activity that was observed in tumor-bearing rats that were not fed supplemental glutamine. Tumor-bearing animals receiving supplemental glutamine had a decreased number of system n carriers (Vmax) in the hepatic plasma membrane compared to that of tumor-bearing animals receiving a control diet; this apparently abrogated the glutamine efflux rate. Glutamine feeding did not alter system n activity in nontumor-bearing controls.


CONCLUSIONS
In the tumor-bearing animal model, system n is modulated by the circulating glutamine concentration. This is the first study that demonstrates the ability of specialized nutrition to "downregulate" transport activity in vivo. Provision of glutamine-enriched diets to the host with cancer may maintain hepatic glutamine levels and prevent host glutamine depletion.
Inoue
Y
Y
Department of Surgery, University of Florida College of Medicine, Gainesville.
Bode
B P
BP
Souba
W W
WW
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane; D004032:Diet; D015536:Down-Regulation; D005354:Fibrosarcoma / Q000378:metabolism; D005973:Glutamine / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D005973:Glutamine