Endoplasmic reticulum stress regulates inflammation in adipocyte of obese rats via toll-like receptors 4 signaling

Objective(s): To explore whether endoplasmic reticulum (ER) stress regulates inflammation in adipose tissue of obese rats via TLR4 signaling. Materials and Methods: Sprague Dawley rats were randomly divided into four groups, and body weight, food intake, and free fatty acids (FFA) were measured. Real-time PCR and Western blot were used to determine mRNA or protein expression of TLR4, TRAF6, IKK beta, TNF-alpha, IL-6, and GRP78. Immunohistochemistry was used to detect GRP78 protein expression. Results: The FFA levels in HFD, HFD+PBA, and HFD+VIPER groups were higher than that in the control group (P<0.05). Compared with the control group, HFD induced GRP78 expression significantly (P<0.05), which could be decreased by ER stress inhibitor but not by TLR4 blocker. The mRNA expression of TLR4, TRAF6, TNF-alpha, and IL-6, and protein levels of TLR4, TNF-alpha, and IKK beta in the HFD group increased significantly compared with the control group (P<0.05), while these changes could be suppressed by PBA or VIPER (P<0.05). The immunohistochemistry staining indicated GRP78 expression in the HFD group was higher than that of the control group, which could be inhibited by PBA or VIPER. Conclusion: HFD could induce inflammation in adipose tissue via ER stress and its downstream TLR4 signaling.