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Hyperlipidemia Modifies Innate Immune Responses to Lipopolysaccharide via the TLR-NF-κB Signaling Pathway

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The objective of this study was to investigate the effect of hyperlipidemia (HLP) on innate immune responses to lipopolysaccharide (LPS). Male New Zealand white rabbits were fed a normal diet (ND) or a high-fat diet (HFD) for 8 weeks. In vivo, the rabbits were injected intravenously with LPS for 24 h. In vitro, peripheral mononuclear cells were collected and stimulated (or unstimulated) with LPS for 24 h. Assay results were analyzed with one-way ANOVA or an equivalent non-parametric test. A P value of 0.05 was considered statistically significant. Despite having no influence in body weight, the HFD intake significantly increased serum lipids, C-reactive protein (CRP), nuclear factor (NF)-κB subunit p65, Toll-like receptor (TLR)-4, SR-A and FAS. Although we found increased circulating tumor necrosis factor (TNF)-α, interleukin (IL)-6, CRP, IL-1β, and IL-10 in the ND-fed rabbits, no significant difference was found in the LPS-stimulated production of TNF-α, IL-6, and CRP in the HFD-fed rabbits. The macrophages harvested from the HFD-fed rabbits developed a blunted inflammatory response, with lower mRNA expression of TNF-α, IL-6, CRP, TLR-4, SR-A, FAS, and Bcl-2 than that expressed by the ND group. In the HFD-fed animals, LPS incubation decreased NF-κB subunit p65 expression, whereas the cytoplasmic phosphorylation of the inhibitor of NF-κB protein was enhanced. These data indicate that HLP displayed a form of innate immune paralysis, including reduced pro- and anti-inflammatory cytokine release to external stimulus, which was related to the altered TLR-NF-κB signaling pathway and altered pro- and anti-apoptotic processes in macrophages.

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Acknowledgment

This study was supported by the National Natural Science Foundation of China (Grant No. 81170973, 30973326). We sincerely thank the members of our laboratory for critical comments and discussion, and Comparative Medicine Facility of Fuzhou General Hospital of Nanjing Military Region for assistance with animal experiments.

The authors have no conflicts of interest to disclose, whether financial or of any other nature.

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Authors and Affiliations

  1. School and Hospital of Stomatology, Fujian Medical University, and Stomatological Key Laboratory of Fujian College and University, Fuzhou, Fujian, China

    Shuai Chen, Gengbing Lin, Lang Lei, Xiaoqing You, Chunfang Wu, Wenjing Xu, Min Huang, Lan Luo, Zhijun Wang, Yanfen Li, Xin Zhao & Fuhua Yan

  2. School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, and School of Stomatology, Nanjing University, Nanjing Stomatological Hospital, 30 Zhongyang Road, Nanjiang, Jiangsu, China

    Fuhua Yan

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  1. Shuai Chen
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Chen, S., Lin, G., Lei, L. et al. Hyperlipidemia Modifies Innate Immune Responses to Lipopolysaccharide via the TLR-NF-κB Signaling Pathway. Inflammation 36, 968–976 (2013). https://doi.org/10.1007/s10753-013-9628-9

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