TLR4 links innate immunity and fatty acid–induced insulin resistance
J. Clin. Invest. Hang Shi, et al. 116:3015 doi:10.1172/JCI28898 [Go to this article.]

Figure 1
FFAs activate TLR4 signaling. (A) FFAs activate TLR4 signaling in transfected 293T cells (n = 6; *P < 0.01). 293T cells were transiently transfected with TLR4/MD-2 expression vectors, with or without dominant negative MyD88 (MyD88-DN), and an NF-κB luciferase reporter and were then treated with a 200 μM oleate/palmitate mixture or 100 ng/ml LPS as a positive control. (B) FFAs cause IκBα degradation and JNK phosphorylation in WT but not TLR4-deficient macrophages. Peritoneal macrophages were isolated and precultured for 4 days before treatment. Cells were treated with 500 μM palmitate over the time course indicated. NS, nonspecific. (C and D) FFAs induce TNF-α and IL-6 mRNA in peritoneal macrophages in WT but not TLR4^–/– mice (n = 4; *P < 0.01). Peritoneal macrophages were treated with 200 μM FFA mixture for 8 hours. Real-time RT-PCR was used to measure mRNA levels. Data are expressed as mean ± SEM.