Fucoidan ameliorates lipid accumulation, oxidative stress, and NF-κB-mediated inflammation by regulating the PI3K/AKT/Nrf2 signaling pathway in a free fatty acid-induced NAFLD spheroid model

作者：Xueru Chu, Xuan Wang, Keqing Feng, Yanzhen Bi, Yongning Xin, Shousheng Liu · 发表于：Lipids in Health and Disease · 年份：2025 · DOI：10.1186/s12944-025-02483-z · 被引用次数：29 · 研究领域：Seaweed-derived Bioactive Compounds、Gut microbiota and health、Liver Disease Diagnosis and Treatment

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Previous studies have reported that fucoidan can relieve obesity and hepatic steatosis in vivo, although the molecular mechanism remains unclear. This study aimed to explore the effect and potential molecular mechanism of fucoidan in NAFLD using the free fatty acid (FFA)-induced NAFLD spheroid model. MATERIALS AND METHODS: The spheroids were constructed by fusing the HepG2 and LX-2 cells. Spheroids and HepG2 cells were stimulated with FFAs and fucoidan, then the intracellular lipid contents and the oxidative stress levels (ROS/MDA/GSH/GR/GPx/NQO1/GCLC/HO-1) were detected. Furthermore, the regulation of PI3K/AKT/Nrf2 pathway and the expression of inflammatory factors (TNF-α and IL-6) were measured. RESULTS: Fucoidan markedly reduced FFA-induced intracellular lipid accumulation in spheroids and HepG2 cells. Notably, fucoidan relieved FFA-induced oxidative stress by reducing the levels of ROS and MDA, and elevating the levels of GSH, GR, and GPx. Furthermore, fucoidan reduced FFA-induced oxidative stress by activating the PI3K/AKT/Nrf2 signaling pathway and by inhibiting ROS-induced P65 NF-κB activation and inflammatory responses via Nrf2 pathway activation. CONCLUSIONS: Our results demonstrated that fucoidan ameliorated FFA-induced lipid accumulation, oxidative stress, and NF-κB-mediated inflammation through the PI3K/AKT/Nrf2 signaling pathway in the spheroid and HepG2 c...