High-fat diet blunts activation of the nuclear factor-kappa B signaling pathway in lipopolysaccharide-stimulated peritoneal macrophages of Wistar rats

Objective: The present study was designed to investigate the effect of a high-fat diet (HFD) on the inflammatory response of peritoneal macrophages. Methods: Male Wistar rats were fed a control diet (n = 12) or an HFD (n = 12) for 12 wk. After euthanasia, peritoneal macrophages were collected and stimulated (or not) with lipopolysaccharide (LPS). Results from the assays using peritoneal macrophages were analyzed with one-way analysis of variance or an equivalent non-parametric test. The level of significance adopted was 0.05. Results: Consumption of the HFD was associated with significant increases in weight gain and fat depots (P < 0.05). Despite having no influence in systemic markers of inflammation, such as interleukin (IL)-6, tumor necrosis factor-a, and plasminogen activator inhibitor-1, the HFD intake significantly decreased insulin sensitivity, as evaluated by the homeostasis model assessment index (P < 0.05). A decreased production of IL-1 beta, IL-6, IL-10, and nitric oxide in response to the LPS stimulation was observed in peritoneal macrophages from the HFD group (P < 0.05). Also, in HFD-fed animals, LPS incubation did not increase IL-1 beta and IL-6 mRNA expression (P < 0.05). These effects were associated with an attenuation of I kappa B inhibitor kinase-beta phosphorylation and nuclear factor-kappa B activation in response to LPS and with a failure to decrease I kappa B inhibitor-alpha expression (P < 0.05). Conclusion: Chronic consumption of an HFD decreased the LPS-induced inflammatory response of peritoneal macrophages, which was associated with a downregulation of the nuclear factor-kappa B signaling pathway. (C) 2013 Elsevier Inc. All rights reserved. (AU)