title: High-fat diet blunts activation of the nuclear factor-κB signaling pathway in lipopolysaccharide-stimulated peritoneal macrophages of Wistar rats.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition, School of Public Health, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Borges
authors.forename: Marco A R
authors.initials: MA
authors.lastname: Vinolo
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Crisma
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Fock
authors.forename: Primavera
authors.initials: P
authors.lastname: Borelli
authors.forename: Julio
authors.initials: J
authors.lastname: Tirapegui
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Rogero
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D059305:Diet, High-Fat; D015536:Down-Regulation; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide