• Charlotte Breuillard, Linda Belabed, Sandra Bonhomme, Marie-Céline Blanc-Quintin, Nathalie Neveux, Rémy Couderc, Jean-Pascal De Bandt, Luc Cynober, and Sylviane Darquy.
• Laboratory of Nutrition Biology, EA 4466, Paris Descartes University, France. charlotte.breuillard@parisdescartes.fr
• Clin Nutr. 2012 Jun 1;31(3):415-21.

Background & AimsExcess weight and type 2 diabetes lead to increased susceptibility to infections. Our aim was to investigate the role of diabetes-induced decreased arginine (Arg) availability and of a possible dysregulation of Arg metabolism in macrophages favoring inflammation and dysimmunity via altered nitric oxide (NO) and cytokine productions.MethodsIsolated peritoneal macrophages from Zucker Diabetic Fatty (ZDF) or lean rats were incubated with increasing Arg concentration (0-2 mM) and Arg metabolism and regulatory properties were studied.ResultsInducible NO synthase (iNOS) expression did not vary with Arg concentration while NO production reached a maximum at 0.5 mM Arg, being significantly lower in macrophages from ZDF rats. Arginase I and II protein levels reached a maximum between 0.25 and 0.5 mM Arg in controls; in macrophages from ZDF rats arginase I was significantly lower and progressively increased up to 2 mM Arg while arginase II was not affected by Arg concentration. In parallel, Arg downregulated TNFα production in both groups and IL-6 only in control.ConclusionsThis in vitro study shows that Arg metabolism is impaired in macrophages from diabetic-obese rats and that improving Arg availability for these cells restores NO production and contributes to the regulation of the inflammatory process.Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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