TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis

Figure 1

TLR4/AP-1 siRNA transfection alleviated systemic and hepatic inflammation. AP1 siRNA (1#, 2#, and 3#) and TLR4 siRNA (2# and 3#) transfection significantly down-regulated the AP1 and TLR4 mRNA expression, respectively. The decreases in the mRNA expression seemed most remarkable in 2# TLR4 siRNA and 3# AP1 siRNA transfection (a). The expression of TLR4 protein was significantly inhibited in the high-fat diet group with either TLR4 (HT) or AP1 (HA) siRNA transfection (b). The expression of F4/80 and Cd11c mRNA was upregulated in the liver of high-fat diet controls (HM) and high-fat diet controls with empty vector transfection (HC), and these changes were attenuated with either TLR4 (HT) or AP1 (HA) siRNA transfection compared with normal diet controls (NC) (c, d). No significant difference was observed in JNK phosphorylation in the liver, but the serum IL-6 and TNF-α levels were elevated in HM and HC, which were attenuated in HT and HA (e, f). AMPK phosphorylation was significantly decreased in the HM and HC, and it was alleviated in HT and HA (g). and compared with the NC group; # and ## compared with the HM group.

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