Resveratrol supplement inhibited the NF-κB inflammation pathway through activating AMPKα-SIRT1 pathway in mice with fatty liver

Nonalcoholic fatty liver disease (NAFLD) is characterized by high levels of nonesterified fatty acids (NEFA), inflammation, and hepatic steatosis. Inflammation plays a crucial role in the development of fatty liver. Resveratrol (RSV) supplement could improve inflammatory response and hepatic steatosis, whereas the underlying mechanism was not well understood. In this study, mice fed with high-fat diet (HFD) exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-alpha, IL-6, and IL-1 beta. Hepatic NF-kappa B inflammatory pathway was over-induced in HFD mice. In vitro, NEFA treatment further increased NF-kappa B pathway activation in mice hepatocytes, which then promoted the synthesis of inflammatory cytokines. Interestingly, RSV treatment significantly inhibited overactivation of NF-kappa B pathway and improved hepatic steatosis. Furthermore, RSV further increased the AMP-activated protein kinase alpha (AMPK alpha) phosphorylation and sirtuin1 (SIRT1) protein levels to inhibit overactivation of NF-kappa B pathway induced by HFD or high levels of NEFA. AMPK alpha or SIRT1 inhibition significantly decreased the improvement effect of RSV on the NF-kappa B pathway induced by high levels of NEFA. Taken together, these findings indicate that RSV supplement decreases the inflammatory level and improves hepatic steatosis through activating AMPK alpha-SIRT1 pathway. Therefore, these data suggested an important clinical application of RSV in preventing NAFLD in humans.