Resveratrol analog piceatannol restores the palmitic acidinduced impairment of insulin signaling and production of endothelial nitric oxide via activation of antiinflammatory and antioxidative heme oxygenase1 in human endothelial cells

Growing evidence suggests that the elevation of free fatty acids, including palmitic acid (PA), are associated with inflammation and oxidative stress, which may be involved in endothelial dysfunction, characterized by the reduced bioavailability of nitric oxide (NO) synthesized from endothelial NO synthase (eNOS). Heme oxygenase1 (HO1) is important in the preservation of NO bioavailability. Piceatannol (Pic), with similar chemical structure to resveratrol, is suggested to possess similar protective effects as resveratrol. In the present study, human umbilical vein endothelial cells (HUVECs), stimulated with PA, were used to examine the endothelial protective effects of Pic. Pic increased the expression of HO1 via nuclear factor erythroid2related factor2 activation in the HUVECs, and decreased the PAinduced secretions of interleukin6 and tumor necrosis factorα, and the formation of reactive oxygen species ROS via inhibition of NFκB activation. Notably, following inhibition of HO1 activity by tin protoporphryinIX, Pic did not prevent cytokine secretion, ROS formation, and NFκB activation in the PAstimulated HUVECs. PA attenuated insulinmediated insulin receptor substrate1 (IRS1) tyrosine phosphorylation, leading to decreased glucose uptake, and phosphorylation of eNOS, leading to a reduction in the production of NO. Pic effectively mitigated the inhibitory effects of PA on the insulinmediated phosphorylation of IRS1 and eNOS, which was not observed following inhibition of HO1 activity. The results of the present study suggested that Pic may have the potential to prevent PAinduced impairment of insulin signaling and eNOS function, by inducing the expression of the antiinflammatory and antioxidant, HO1.