Dietary Nε-(carboxymethyl)lysine is a trigger of non-alcoholic fatty liver disease under high-fat consumption.

The irreversible glycation of proteins produces advanced glycation end products (AGEs) which are triggered to bind the receptor for AGE (RAGE), thereby activating mitogen-activated protein kinase/nuclear factor-κB signaling pathway and stimulating proinflammatory cytokines, ultimately leading to chronic disorders. In this study, we focus the promoting effect of Nε-carboxymethyl-lysine (CML), one of the most dietary AGEs, on non-alcoholic fatty liver disease (NAFLD) and evaluated NAFLD-related biomarkers. Oxidative stress and hepatic steatosis were assessed in oleic acid (OA)-induced HepG2 cells. Using OA-induced HepG2 cells, we show that CML results in oxidative stress and steatosis and drives major changes in hepatic lipid metabolism. Administration of CML exacerbated NAFLD-related symptoms by increasing body and liver weight gain, serum alanine aminotransferase and lipid levels, and insulin resistance in mild high-fat diet-induced mice. Moreover, hepatic histological analysis data, such as staining, western blotting, and RNA-seq, indicate that CML aggravates NAFLD in association with activation of the de novo lipogenesis pathway, consistent with the in vitro assays. Our findings could contribute to model studies related to the prevention and treatment of NAFLD progression due to excessive consumption of dietary AGEs.