EETs modulate NF-κB signaling and alleviate STZ-induced chronic inflammation in type 2 diabetes

Abstract

ABSTRACT Epoxyeicosatrienoic acids (EETs) have shown preventive effects against various metabolic diseases. The objective of this study was to investigate the effects and mechanisms of EETs onT2DM in rats. The rats were divided into an T2DM group and intervention groups that received 11,12-EET, 14,15-EET and TPPU daily for 30days. Serum concentrations of TNF-α, IL-6, IL-10 and Arg-1 were measured using ELISA. The results showed that EETs and TPPU effectively reduced the concentrations of inflammatory factors (P＜0.05). Histopathologic examination of epididymal fat and liver tissues by HE staining demonstrated that EETs and TPPU significantly improved the morphology and structure of adipose and liver cells. Immunohistochemical analysis of epididymal adipose tissue indicated that both EETs and TPPU significantly inhibited macrophage aggregation. Quantitative PCR and Western blot analyses showed that EETs and TPPU significantly inhibited the NF-κB signaling pathway at both the mRNA and protein levels; and These findings suggest that EETs may reduce inflammation in T2DM rats by modulating macrophage aggregation through inhibition of the NF-κB signaling.