Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker Rat

Authors

  • Marie-Céline Blanc,

    1. Laboratoire de Biologie de la Nutrition, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris 5—René Descartes, Paris, France
    2. Laboratoire de Biochimie A, Hôtel-Dieu, AP-HP, Paris, France
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  • Christophe Moinard,

    1. Laboratoire de Biologie de la Nutrition, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris 5—René Descartes, Paris, France
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  • Aurélie Béziel,

    1. Laboratoire de Biologie de la Nutrition, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris 5—René Descartes, Paris, France
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  • Sylviane Darquy,

    1. Laboratoire de Biologie de la Nutrition, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris 5—René Descartes, Paris, France
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  • Luc Cynober,

    1. Laboratoire de Biologie de la Nutrition, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris 5—René Descartes, Paris, France
    2. Laboratoire de Biochimie A, Hôtel-Dieu, AP-HP, Paris, France
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  • Jean-Pascal De Bandt

    Corresponding author
    1. Laboratoire de Biologie de la Nutrition, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris 5—René Descartes, Paris, France
    2. Laboratoire de Biochimie A, Hôtel-Dieu, AP-HP, Paris, France
    • Laboratoire de Biologie de la Nutrition, EA 2498, Faculté des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75270 Paris Cedex 06, France.
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  • This work has been presented in an abstract form at the 2002 Nutrition Week, San Diego, February 2002.

Abstract

Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin-resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 μg/ml), productions of tumour necrosis factor α (TNFα) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 ± 1,174 vs. 2 mM: 198 ± 31 μM/mg protein/24 h; P < 0.05), but not in those from obese rats, when glutamine was added. TNFα production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFα production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 ± 450 vs. 2 mM: 810 ± 90 μM/mg protein/3 h; P < 0.05). These results suggest that abnormalities in cell signalling or in arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFα production and increased NO release, may contribute to increased susceptibility to infection in insulin-resistant states. © 2005 Wiley-Liss, Inc.

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