Starvation and Endotoxin Act Independently and Synergistically to Coordinate Hepatic Glutamine Transport

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Abstract

Objective

Because hepatic glutamine transport is markedly enhanced during critical illness, we tested the hypothesis that nutrient starvation and endotoxemia act coordinately to augment transport activity.

Design

Fed or starved (48 hours) rats received Escherichia coli endotoxin (LPS, 10 mg/kg of body weight, intraperitoneally) or saline before hepatocyte isolation for measurement of glutamine transport.

Materials and Methods

Hepatocytes were isolated from fed or fasted rats 4 hours after LPS treatment. [sup 3 H]glutamine uptake was measured and normalized to cellular protein. Data (mean +/- standard deviation, three separate determinations) were analyzed by Student's t test and analysis of variance.

Main Results

Starvation induced a 1.6-fold increase in glutamine transport, while LPS treatment of fed rats increased transport activity 2.6-fold. Treatment of fasted animals with LPS induced a sixfold increase in glutamine transport. Kinetically, this effect in endotoxemic starved rats was mediated by both an increase in System N Vmax and the induction of a high affinity System A amino acid carrier which transports glutamine.

Conclusions

Starvation and endotoxemia regualte hepatocyte glutamine transport independently and synergistically. This hepatic response provides glutamine and other amino acids to support key metabolic pathways in the liver during critical illness.

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