Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways

Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated wion and protein-protein interaction were determined by western blotting and ith PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-alpha, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expressimmunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-alpha, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKK beta, p-I kappa B alpha, p-p65 expression, and p-I kappa B alpha-IKK beta interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-kappa B inhibitor PDTC showed similar effect on PA-induced secretion of TNF-alpha, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin triggered expression of p-IRS-1(Tyr), p-PI3K, p-ART, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKK beta pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. (C) 2016 Elsevier Ltd. All rights reserved.