TMAO Stimulate Inflammation and Lipid Accumulation via NF-κB Signaling Pathway in Nonalcoholic Fatty Liver Disease

Abstract

Background Nonalcoholic fatty liver disease (NAFLD) is a common disease and it is commonly associated with obesity. Trimethylamine N-oxide (TMAO) is a metabolite of intestinal flora generated in liver by flavin-containing monooxygenase 3 (FMO3), which has been widely studied in cardiovascular diseases and obesity. However, the mechanism of TMAO reacted on liver remains unclear. This study aimed to determine TMAO activated hepatitis inflammation and lipid accumulation which was associated with nuclear factor kappa B (NF-κB) signaling pathway in vitro. ResultsThe present study showed that TMAO in 50μM markedly increased the LO2 cells function and decreased the cells inflammation. However, over the concentration of 200μM in TMAO, cells inflammation was increased and function was declined apparently. In addition, TMAO promoted lipid accumulation. Mechanistically, this change was accompanied by the activation of NF-κB signaling pathway. Furthermore, blocking NF-κB by SN50 was significantly increased in lipid accumulation and apoptosis. SN50 was markedly decreased the protein expression stimulating by TMAO.ConclusionsOverall, the result suggested that TMAO promotes cells inflammation and lipid accumulation in hepatocytes and it might be associated with NF-κB signaling pathway.