Reduced caloric intake during endotoxemia reduces arginine availability and metabolism

Abstract

Background: Inadequate caloric intake increases the risk of sepsisinduced complications. Metabolic changes during sepsis indicate that the availability of the amino acid L-arginine decreases. Availability of arginine may further decrease during reduced caloric intake, which thereby limits the adaptive response of arginine-nitric oxide metabolism during sepsis. Objective: We tested the hypothesis that reduced caloric intake during endotoxemia, as an experimental model for sepsis, further reduces arginine availability. Design: In a randomized trial, a 7-d reduced caloric intake feed regimen (RE; n = 9) was compared with a normal control feed regimen (CE; n = 9), before 24 h of endotoxemia, as a model for sepsis. Whole-body arginine-nitric oxide metabolism and protein metabolism were measured by using a stable-isotope infusion of [15N2]arginine, [13C-2H 2]citrulline, [2H5]phenylalanine, and [2H 2]tyrosine. Plasma pyruvate and lactate concentrations were determined by fully automated HPLC. Results: Pre-endotoxin arginine appearance was significantly lower in the RE group than in the CE group (P = 0.002). During endotoxemia, arginine appearance increased in the CE animals but not in the RE animals (P = 0.04). In addition, nitric oxide production was significantly lower in the RE animals (P < 0.0001). Protein synthesis was significantly lower at the start of endotoxin infusion (P < 0.05) and remained lower during endotoxemia in the RE group than in the CE group (P < 0.001). The lactate:pyruvate ratio was not higher in the RE group than in the CE group before endotoxemia but increased significantly during endotoxemia in the RE group (P = 0.04). Conclusion: A well-nourished condition before prolonged endotoxemia results in a better ability to adapt to endotoxin-induced metabolic deterioration of arginine-nitric oxide metabolism than does reduced caloric intake before endotoxemia. © 2010 American Society for Nutrition.