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.

Objective Current research has reported that obesity is a chronic inflammatory state, which is closely related with excessive accumulation of free fatty acid, while the specific mechanism that high level of FFA causes inflammation is not very clear. Thus, our research intended to observe the high FFA effects on TLR9/KLF4 expression and the downstream inflammatory factors, to explore the mechanism of inflammatory response suppressed by TLR9/KLF4. Methods qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of TLR9, KLF4, and key inflammation-related factors. ELISA was used to detect the release level of inflammatory cytokines. The triglyceride (TG) and glucose (GLU) testing cassettes were used to detect the TG and GLU levels in culture medium. Results In the omental tissue of obese individuals (OB), we found that TLR9, KLF4, mRNA, and the protein expression levels were lower than those of the normal weight control (NC) group. Similarly, in the omental tissue of high-fat diet (HFD) rats, we found that the mRNA expression levels of TLR9 and KLF4 were lower than those of the normal diet control group. In mature adipocytes, we found that KLF4 played an important anti-inflammatory role; moreover, PA can promote the development of inflammation by inhibiting KLF4 expression; TLR9 has a positive regulation function on KLF4 expression, but unrelated to PA. Conclusions TLR9/KLF4 is involved in regulating FFA-induced adipocyte inflammation.

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