title: Arginine availability modulates arginine metabolism and TNFα production in peritoneal macrophages from Zucker Diabetic Fatty rats.
abstract: OBJECTIVE
  Excess 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.
  
  
  METHODS
  Isolated 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.
  
  
  RESULTS
  Inducible 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Laboratory of Nutrition Biology, EA 4466, Paris Descartes University, France. charlotte.breuillard@parisdescartes.fr
authors.forename: Charlotte
authors.initials: C
authors.lastname: Breuillard
authors.forename: Linda
authors.initials: L
authors.lastname: Belabed
authors.forename: Sandra
authors.initials: S
authors.lastname: Bonhomme
authors.forename: Marie-Céline
authors.initials: MC
authors.lastname: Blanc-Quintin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Neveux
authors.forename: Rémy
authors.initials: R
authors.lastname: Couderc
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: De Bandt
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.forename: Sylviane
authors.initials: S
authors.lastname: Darquy
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000097:blood / Q000378:metabolism*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D009994:Osmolar Concentration; D051381:Rats; D011924:Rats, Zucker; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C113162:Arg2 protein, rat; D001119:Arginase; C542908:arginase I, rat