Endoplasmic reticulum stress regulates inflammation in adipocyte of obese rats via toll-like receptors ۴ signaling

Objective(s): To explore whether endoplasmic reticulum (ER) stress regulates inflammation in adipose tissue of obese rats via TLR۴ 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 TLR۴, TRAF۶, IKKβ, TNF-α, IL-۶, and GRP۷۸. Immunohistochemistry was used to detect GRP۷۸ protein expression. Results: The FFA levels in HFD, HFD+PBA, and HFD+VIPER groups were higher than that in the control group (P<۰.۰۵). Compared with the control group, HFD induced GRP۷۸ expression significantly (P<۰.۰۵), which could be decreased by ER stress inhibitor but not by TLR۴ blocker. The mRNA expression of TLR۴, TRAF۶, TNF-α, and IL-۶, and protein levels of TLR۴, TNF-α, and IKKβ in the HFD group increased significantly compared with the control group (P<۰.۰۵), while these changes could be suppressed by PBA or VIPER (P<۰.۰۵). The immunohistochemistry staining indicated GRP۷۸ 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 TLR۴ signaling.

Keywords:

Adipocyte , Endoplasmic reticulum stress , Inflammation , Obesity , Toll-like receptor ۴