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

Nutrition. 2013 Feb;29(2):443-9. doi: 10.1016/j.nut.2012.06.008. Epub 2012 Oct 22.

Abstract

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-α, 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-1β, 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-1β and IL-6 mRNA expression (P < 0.05). These effects were associated with an attenuation of IκB inhibitor kinase-β phosphorylation and nuclear factor-κB activation in response to LPS and with a failure to decrease IκB inhibitor-α 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-κB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Cells, Cultured
  • Diet, High-Fat*
  • Down-Regulation
  • Inflammation / metabolism
  • Insulin Resistance
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides / metabolism
  • Macrophages, Peritoneal / metabolism*
  • Male
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Nitric Oxide / blood
  • Phosphorylation
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / blood
  • Weight Gain

Substances

  • Biomarkers
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Nitric Oxide