| Summary: | Saturated fatty acids (SFAs) can directly stimulate innate immune responses, thereby exacerbating inflammatory aspects of metabolic syndrome. Dietary SFAs act as ligands of Toll-like receptor 4 (TLR4), triggering associated signaling pathways. In this study, we investigated the role of TLR4 in palm oil SFA-associated inflammatory cytokine gene expression in monocytes/macrophages and adipose tissue using TLR4 -overexpressing genetically modified sheep. SFA stimulation resulted in upregulation of interleukin-6 ( IL-6 ), tumor necrosis factor-α ( TNF-α ), interleukin-8 ( IL-8 ), interferon-γ ( IFN-γ ), and interleukin-10 ( IL-10 ), and TLR4 overexpression enhanced such SFA-induced inflammatory cytokine expression. Moreover, SFAs markedly activated MyD88-dependent signaling, including IL-1 receptor–associated kinase 4 ( IRAK4 ), TNF receptor–associated factor 6 ( TRAF6 ), and nuclear factor-κB ( NF-κB ). Taken together, our results indicate that TLR4 overexpression enhances the SFA-induced inflammatory response through MyD88-dependent signaling in monocytes/macrophages and adipose tissue.
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