Palmitic acid up regulates Gal-3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF-κB

xlomafota13 shared this article with you from Inoreader Palmitic acid up regulates Gal-3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF-κB Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1028. doi: 10.3892/etm.2021.10460. Epub 2021 Jul 18. ABSTRACT Insulin resistance is the main sign of type 2 diabetes mellitus and is often accompanied by the infiltration of inflammatory factors. These inflammatory factors are mainly produced and secreted by macrophages. The purpose of the current study was to explore the relationship between macrophages and insulin resistance, and to determine its underlying mechanism. The insulin resistance of macrophages was induced by palmitic acid (PA) in vitro. The glucose uptake rate of macrophages, the expression levels of inflammatory cytokines and the expression levels of insulin resistance-related proteins were detected. The protein expression levels of Krüppel-like factor 4 (KLF4), toll-like receptor 4 (TLR4), NF-κB and Galectin-3 (Gal-3) were detected via western blotting and recovery experiments were performed by combining the Gal-3 and TLR4 inhibitor s GB1107 and TAK242. The results revealed that PA-induced macrophages demonstrated insulin resistance. Additionally, KLF4 protein was inhibited and the sugar uptake rate was significantly lower than that of the control group. Western blotting and immunofluorescence assays revealed that the expression of Gal-3 in PA-induced macrophages was significantly upregulated. The addition of the Gal-3 inhibitor GB1107 significantly increased glucose utilization and reduced insulin resistance in PA-treated cells. Inhibitor of TLR4 inhibited the protein expression level of the TLR4/NF-κB pathway. In conclusion, PA promoted the TLR4/phosphorylated-NF-κB signaling pathway by inhibiting KLF4, promoted the upregulation of Gal-3 expression and improved the insulin resistance of macrophages. PMID:34373714 | PMC:PMC8343820 | DOI:10.3892/etm.2021.10460 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.