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 collect...

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Published in:Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2013-02, Vol.29 (2), p.443-449
Main Authors: Borges, Maria C., M.Sc, Vinolo, Marco A.R., Ph.D, Crisma, Amanda R., Ph.D, Fock, Ricardo A., Ph.D, Borelli, Primavera, Ph.D, Tirapegui, Julio, Ph.D, Curi, Rui, Ph.D, Rogero, Marcelo M., Ph.D
Format: Article
Language:English
Subjects:
analysis of variance
Animals
Biological and medical sciences
Biomarkers - blood
body fat
Cells, Cultured
Diet, High-Fat
Down-Regulation
euthanasia
experimental design
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Gastroenterology and Hepatology
gene expression
High-fat diet
Inflammation
Inflammation - metabolism
Insulin Resistance
Interleukin-10 - blood
Interleukin-1beta - blood
Interleukin-6 - blood
Lipopolysaccharides - metabolism
Macrophages
Macrophages, Peritoneal - metabolism
Male
messenger RNA
NF-kappa B - genetics
NF-kappa B - metabolism
nitric oxide
Nitric Oxide - blood
Nuclear factor-κB
Phosphorylation
plasminogen activator
Plasminogen Activator Inhibitor 1 - metabolism
Rat
Rats
Rats, Wistar
Signal Transduction
Tumor Necrosis Factor-alpha - blood
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Weight Gain
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Summary: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.
ISSN:0899-9007
1873-1244
DOI:10.1016/j.nut.2012.06.008