Lee Hye-Bin, Choi Ju Hyeong, Kim Donghwan, Lee Kwang-Won, Ha Sang Keun, Lee Sang-Hoon, Park Ho-Young
Food Functionality Research Division, Korea Food Research Institute, Jeollabuk-do, 55365, Republic of Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
Food Chem Toxicol. 2023 Oct;180:114010. doi: 10.1016/j.fct.2023.114010. Epub 2023 Aug 29.
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 N-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.
蛋白质的不可逆糖基化会产生晚期糖基化终末产物（AGEs），这些产物会与AGE受体（RAGE）结合，从而激活丝裂原活化蛋白激酶/核因子-κB信号通路并刺激促炎细胞因子，最终导致慢性疾病。在本研究中，我们聚焦于膳食中最常见的AGEs之一N-羧甲基赖氨酸（CML）对非酒精性脂肪性肝病（NAFLD）的促进作用，并评估了与NAFLD相关的生物标志物。在油酸（OA）诱导的HepG2细胞中评估氧化应激和肝脂肪变性。利用OA诱导的HepG2细胞，我们发现CML会导致氧化应激和脂肪变性，并驱动肝脏脂质代谢的重大变化。在轻度高脂饮食诱导的小鼠中，给予CML会通过增加体重和肝脏重量、血清丙氨酸转氨酶和脂质水平以及胰岛素抵抗，加剧与NAFLD相关的症状。此外，肝脏组织学分析数据，如染色、蛋白质印迹和RNA测序，表明CML与从头脂肪生成途径的激活相关，从而加重NAFLD，这与体外实验结果一致。我们的研究结果可能有助于开展与预防和治疗因过量摄入膳食AGEs导致的NAFLD进展相关的模型研究。
