Resveratrol modulates autophagy and NF-κB activity in a murine model for treating non-alcoholic fatty liver disease

Abstract

In this study, we aimed to investigate the therapeutic effects and involved mechanisms of resveratrol on an established non-alcoholic fatty liver disease (NAFLD) murine model. Wild-type and autophagic mediator ULK1 heterozygous knockout mice were induced to have NAFLD by high-fat diet for 8weeks. After that, resveratrol treatment was applied with the high-fat diet feeding for another 4weeks. Typical features of NAFLD, including histological changes, fibrosis, insulin resistance, oxidative status, and inflammation were characterized. After-treatment with resveratrol showed ameliorative effects on all measured features of NAFLD, from histology, insulin resistance, glucose tolerance to oxidative stress and inflammation. resveratrol treatment also reduced the activity of nuclear factor-κB (NF-κB) through the restoration of its inhibitor IκBα. Partial inhibition of ULK1 expression impaired the ameliorative effects of resveratrol on hepatic histology, fibrosis, oxidative status, inflammation, and NF-κB activity. In conclusion, resveratrol improved NAFLD-caused hepatic injury partially through regulating autophagic and IκBα-NF-κB pathways.

Keywords: ALT; AMP-activated protein kinase; AMPK; AST; Autophagy; GPx; GTT; HCC; IL; ITT; IκBα; MDA; NAFLD; NASH; NF-κB; PBS; Resveratrol; SREBP-1c; TNF; ULK1; UNC-51-like kinase 1; alanine aminotransferase; aspartate aminotransferase; glucose tolerance test; glutathione peroxidase; hepatocellular carcinoma; inhibitor of kappaB alpha; insulin tolerance test; interleukin; malondialdehyde; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; nuclear factor-kappaB; phosphate buffered solution; sterol regulatory element-binding protein-1c; tumor necrosis factor.