Abstract
Objective To investigate the role and possible molecular mechanism of Krüppel-like factor 7 (KLF7) in the TLR4/NF-κB/IL-6 inflammatory signaling pathway activated by free fatty acids (FFA). Methods The mRNA and protein expression levels of KLF7 and the factors of TLR4/NF-κB/IL-6 inflammatory signal pathways were detected by qRT-PCR and Western blotting after cell culture with different concentrations of palmitic acid (PA). The expression of KLF7 or TLR4 in adipocytes was upregulated or downregulated; after that, the mRNA and protein expression levels of these key factors were detected. KLF7 expression was downregulated while PA stimulated adipocytes, and then the mRNA and protein expressions of KLF7/p65 and downstream inflammatory cytokine IL-6 were detected. The luciferase reporter assay was used to determine whether KLF7 had a transcriptional activation effect on IL-6. Results (1) High concentration of PA can promote the expression of TLR4, KLF7, and IL-6 in adipocytes. (2) TLR4 positively regulates KLF7 expression in adipocytes. (3) KLF7 positively regulates IL-6 expression in adipocytes. (4) PA promotes IL-6 expression via KLF7 in adipocytes. (5) KLF7 has a transcriptional activation on IL-6. Conclusion PA promotes the expression of the inflammatory cytokine IL-6 by activating the TLR4/KLF7/NF-κB inflammatory signaling pathway. In addition, KLF7 may directly bind to the IL-6 promoter region and thus activate IL-6.
Highlights
Obesity has been reported to be a chronic low-inflammation state
Adipocytes were stimulated with different concentrations of palmitic acid (PA) for 48 h, and the expression of TLR4, Krüppel-like factor 7 (KLF7), and IL-6 was detected
The TLR4, KLF7, p65, phosphorylation p65, and IL-6 protein expression levels were significantly increased after 48 h of stimulation with 100 μmol/L PA (Figures 1(j) and 1(k))
Summary
The release of adipocyte inflammatory factors is closely related to the increase of blood free fatty acid levels caused by obesity [1, 2]. Toll-like receptors (TLRs) play an important role in the inflammatory signaling pathway of the innate immune response [5]. Studies have shown that high levels of free fatty acids in the obese state induce immune inflammatory responses by binding to the adipocyte membrane receptor TLR4 and induce the expression and secretion of inflammatory-related factors, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) [6,7,8,9,10,11,12]. The above-cited reports indicate that KLF7 may be involved in regulating the lipid metabolism and endocrine function of adipocytes.
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