Arginine availability modulates arginine metabolism and TNFα production in peritoneal macrophages from Zucker Diabetic Fatty rats

Abstract

Background & aims: 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.