Mechanisms of electroacupuncture in improving obesity-induced insulin resistance via TLR4/NF-κB inflammatory pathway in liver

Abstract

To investigate the effect of electroacupuncture (EA) on the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) inflammatory pathway in the liver of obese rats with insulin resistance, and explore its mechanism. Male Wistar rats were randomly divided into a normal group (n=15) and an experimental group (n=30). The obesity-induced insulin resistance model was induced by the high-fat diet (HFD) in rats of the experimental group for 8 weeks. Subsequently, the model rats were further divided into a model group (n=15) and an EA group (n=15). EA was applied at "Zhongwan "(CV12), "Guanyuan" (CV4), "Zusanli "(ST36) and "Fenglong "(ST40) in the EA group for 10 min, three times a week for 8 weeks. The body weight of rats in each group was measured before intervention and at the 2nd, 4th, 6th, and 8th weeks during the intervention. Glucose infusion rate (GIR) was measured by glucose clamp test before and after treatment. After treatment, fast blood glucose (FBG) was detected by the glucometer, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The contents of fasting insulin (FINS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were determined by ELISA. The protein expressions of TLR4, IκB kinase β (IKKβ), phosphorylated IKKβ (p-IKKβ), NF-κB p65, and TNF-α related to the TLR4/NF-κB signaling pathway in the liver of rats were detected by Western blot. Compared with the normal group, the body weight, HOMA-IR levels, serum levels of FINS, TNF-α, and IL-6 were up-regulated (P<0.01), and the GIR level was down-regulated (P<0.01), the protein expressions of TLR4, IKKβ, p-IKKβ, NF-κB p65 and TNF-α in liver tissues were increased(P<0.05) in the model group. Compared with the model group, the EA group showed weight loss from the 6th week, and the HOMA-IR levels，serum levels of FINS, TNF-α, and IL-6 were decreased(P<0.01, P<0.05), the GIR level was up-regulated (P<0.01), the protein expressions of TLR4, IKKβ, p-IKKβ, NF-κB p65 and TNF-α in liver tissues were down-regulated (P<0.05). EA can reduce the inflammatory response and improve peripheral insulin sensitivity by inhibiting the TLR4/NF-κB pathway in liver tissues of obese rats with insulin resistance, showing a good regulatory effect on insulin resistance induced by obesity.